PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 17339023-0 2007 The path to insulin resistance: paved with ceramides? Ceramides 43-52 insulin Homo sapiens 12-19 17650308-11 2007 Meanwhile, it releases abundant fatty acid products (e.g. diacylglycerol, ceramides) that impair insulin actions via signal transduction, thereby causing MIR. Ceramides 74-83 insulin Homo sapiens 97-104 17285001-4 2007 RECENT FINDINGS: Recent studies have suggested that local accumulation of fat metabolites such as ceramides, diacylglycerol or acyl-CoA, inside skeletal muscle and liver, may activate a serine kinase cascade leading to defects in insulin signalling and glucose transport. Ceramides 98-107 insulin Homo sapiens 230-237 17158207-8 2007 Effects of TNFalpha and C6 on insulin-stimulated phosphorylation of glycogen synthase kinase 3beta were prevented by myriocin and tautomycin, a PP1 inhibitor, further implicating a de novo ceramide-PP1 pathway. Ceramides 189-197 insulin Homo sapiens 30-37 17724577-1 2007 AIMS/HYPOTHESIS: Intramyocellular lipids, including ceramide, a second messenger in the sphingomyelin signalling pathway, might contribute to the development of insulin resistance. Ceramides 52-60 insulin Homo sapiens 161-168 17724577-11 2007 Muscle ceramide was related to insulin sensitivity independently of other muscle lipid fractions. Ceramides 7-15 insulin Homo sapiens 31-38 17620421-11 2007 Ceramides or their metabolites could contribute to adverse effects of long-chain fatty acids on insulin resistance and inflammation. Ceramides 0-9 insulin Homo sapiens 96-103 17337731-0 2007 Key role for ceramides in mediating insulin resistance in human muscle cells. Ceramides 13-22 insulin Homo sapiens 36-43 17337731-1 2007 Elevated non-esterified fatty acids, triglyceride, diacylglycerol, and ceramide have all been associated with insulin resistance in muscle. Ceramides 71-79 insulin Homo sapiens 110-117 17337731-8 2007 Insulin resistance was also caused by cell-permeable analogues of ceramide, and palmitate-induced resistance was blocked in the presence of inhibitors of de novo ceramide synthesis. Ceramides 66-74 insulin Homo sapiens 0-7 17337731-8 2007 Insulin resistance was also caused by cell-permeable analogues of ceramide, and palmitate-induced resistance was blocked in the presence of inhibitors of de novo ceramide synthesis. Ceramides 162-170 insulin Homo sapiens 0-7 17337731-10 2007 Our data are consistent with ceramide being the agent responsible for insulin resistance caused by palmitate exposure. Ceramides 29-37 insulin Homo sapiens 70-77 17219404-0 2007 Fatty acid-induced defects in insulin signalling, in myotubes derived from children, are related to ceramide production from palmitate rather than the accumulation of intramyocellular lipid. Ceramides 100-108 insulin Homo sapiens 30-37 17219404-8 2007 In summary, palmitate appears to cause insulin resistance in children"s myotubes via its metabolism to ceramide, and this process appears unrelated to IMCL formation and is ameliorated by oleate. Ceramides 103-111 insulin Homo sapiens 39-46 17339023-3 2007 (2007) provide pharmacological and genetic evidence that ceramide plays a key role in the development of insulin resistance induced by these factors. Ceramides 57-65 insulin Homo sapiens 105-112 17339025-6 2007 Second, they identify enzymes required for ceramide synthesis as therapeutic targets for combating insulin resistance caused by nutrient excess or glucocorticoid therapy. Ceramides 43-51 insulin Homo sapiens 99-106 15774472-9 2005 Moreover, these FFAs stimulated the de novo synthesis of ceramide and sphingosine, two sphingolipids shown previously to inhibit insulin action. Ceramides 57-65 insulin Homo sapiens 129-136 17259384-8 2007 We propose that ceramide and oxidative stress can each affect two independent arms of insulin signaling to GLUT4 at distinct steps, Rac-GTP loading and Akt phosphorylation. Ceramides 16-24 insulin Homo sapiens 86-93 17259384-0 2007 Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Ceramides 0-8 insulin Homo sapiens 30-37 17259384-0 2007 Ceramide- and oxidant-induced insulin resistance involve loss of insulin-dependent Rac-activation and actin remodeling in muscle cells. Ceramides 0-8 insulin Homo sapiens 65-72 17242494-1 2006 Ceramide is involved in the pathogenesis of insulin resistance in skeletal muscles of humans and rodents. Ceramides 0-8 insulin Homo sapiens 44-51 17242494-2 2006 However, there are conflicting reports in the literature on the effect of thiazolidinediones (a new class of insulin sensitizing drugs) on skeletal muscle ceramide content. Ceramides 155-163 insulin Homo sapiens 109-116 16396984-0 2006 Ciliary neurotrophic factor prevents acute lipid-induced insulin resistance by attenuating ceramide accumulation and phosphorylation of c-Jun N-terminal kinase in peripheral tissues. Ceramides 91-99 insulin Homo sapiens 57-64 16754199-0 2006 Ceramide mediates TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes. Ceramides 0-8 insulin Homo sapiens 36-43 16754199-3 2006 A short-chain ceramide analogue, C2-ceramide, precluded insulin-induced GLUT4 mRNA accumulation and GLUT4-chloramphenicol acetyltransferase (CAT) full promoter activation. Ceramides 14-22 insulin Homo sapiens 56-63 16754199-4 2006 Moreover, inhibition of the ceramide biosynthesis with fumonisin B, which inhibits ceramide synthase, completely restored insulin-induced GLUT4 mRNA and protein accumulation as well as GLUT4-CAT transactivation in the presence of TNF-alpha. Ceramides 28-36 insulin Homo sapiens 122-129 16754199-8 2006 Our results indicate that de novo ceramide produced by TNF-alpha-induced insulin resistance on GLUT4 gene expression in brown adipocytes by interfering C/EBP-alpha expression, a transcription factor essential for the expression of GLUT4. Ceramides 34-42 insulin Homo sapiens 73-80 16497175-7 2006 Thus, leptin and adiponectin resistance may be an initiating factor in the accumulation of intramuscular lipids, such as diacylglycerol and ceramide, and the ensuing development of insulin resistance. Ceramides 140-148 insulin Homo sapiens 181-188 16445986-0 2006 Ceramides in insulin resistance and lipotoxicity. Ceramides 0-9 insulin Homo sapiens 13-20 16445986-7 2006 In this review, I will evaluate the contribution of ceramides in the development of insulin resistance and the complications associated with metabolic diseases. Ceramides 52-61 insulin Homo sapiens 84-91 15448091-2 2004 Here we investigated 1) whether ceramide synthesis, which we reported to mediate fatty acid inhibition of insulin gene expression, also inhibits insulin secretion and 2) whether fatty acid inhibition of insulin secretion involves the generation of reactive oxygen species (ROS), nitric oxide (NO), or prostaglandin E(2) (PGE(2)). Ceramides 32-40 insulin Homo sapiens 106-113 15111489-1 2004 In vitro studies revealed that insulin resistance might be associated with the intracellular formation of ceramide, the second messenger in the sphingomyelin signaling pathway. Ceramides 106-114 insulin Homo sapiens 31-38 15111489-7 2004 Insulin sensitivity was related to total ceramide content (r = -0.49, P = 0.01) and to ceramide consisting of palmitic (r = -0.48, P = 0.011), palmitoleic (r = -0.45, P = 0.019), mirystic (r = -0.42, P = 0.028), and nervonic acid (r = -0.39, P = 0.047). Ceramides 41-49 insulin Homo sapiens 0-7 15111489-7 2004 Insulin sensitivity was related to total ceramide content (r = -0.49, P = 0.01) and to ceramide consisting of palmitic (r = -0.48, P = 0.011), palmitoleic (r = -0.45, P = 0.019), mirystic (r = -0.42, P = 0.028), and nervonic acid (r = -0.39, P = 0.047). Ceramides 87-95 insulin Homo sapiens 0-7 15111489-11 2004 A relationship with the decrease in insulin sensitivity was also observed for ceramides consisting of palmitic (r = -0.68, P = 0.03) and linoleic (r = -0.66, P = 0.038) acid. Ceramides 78-87 insulin Homo sapiens 36-43 14505487-12 2003 The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1. Ceramides 109-117 insulin Homo sapiens 91-98 15294058-4 2004 Fatty acyl-CoA, ceramides and diacylglycerols are known to directly alter various aspects of the insulin signalling cascade. Ceramides 16-25 insulin Homo sapiens 97-104 14693694-2 2004 Ceramides, either generated via activation of sphingomyelinase or produced by de novo synthesis, induce insulin resistance in cultured cells by inhibitory effects on insulin signaling. Ceramides 0-9 insulin Homo sapiens 104-111 14693694-2 2004 Ceramides, either generated via activation of sphingomyelinase or produced by de novo synthesis, induce insulin resistance in cultured cells by inhibitory effects on insulin signaling. Ceramides 0-9 insulin Homo sapiens 166-173 14693694-11 2004 This twofold increase in ceramide may be involved in the decrease in Akt phosphorylation observed after insulin infusion and could theoretically play a role in the reduced ability of insulin to stimulate glucose uptake in skeletal muscle from obese subjects. Ceramides 25-33 insulin Homo sapiens 104-111 14693694-11 2004 This twofold increase in ceramide may be involved in the decrease in Akt phosphorylation observed after insulin infusion and could theoretically play a role in the reduced ability of insulin to stimulate glucose uptake in skeletal muscle from obese subjects. Ceramides 25-33 insulin Homo sapiens 183-190 14505487-12 2003 The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1. Ceramides 109-117 insulin Homo sapiens 160-167 11270673-0 2001 Ceramide impairs the insulin-dependent membrane recruitment of protein kinase B leading to a loss in downstream signalling in L6 skeletal muscle cells. Ceramides 0-8 insulin Homo sapiens 21-28 12525490-0 2003 A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. Ceramides 11-19 insulin Homo sapiens 66-73 12525490-3 2003 These saturated FFAs concomitantly induced the accumulation of ceramide and diacylglycerol, two products of fatty acyl-CoA that have been shown to accumulate in insulin-resistant tissues and to inhibit early steps in insulin signaling. Ceramides 63-71 insulin Homo sapiens 161-168 12525490-3 2003 These saturated FFAs concomitantly induced the accumulation of ceramide and diacylglycerol, two products of fatty acyl-CoA that have been shown to accumulate in insulin-resistant tissues and to inhibit early steps in insulin signaling. Ceramides 63-71 insulin Homo sapiens 217-224 12525490-7 2003 Collectively these results identify ceramide as a necessary and sufficient intermediate linking saturated fats to the inhibition of insulin signaling. Ceramides 36-44 insulin Homo sapiens 132-139 12532151-0 2003 Cell-permeable ceramides increase basal glucose incorporation into triacylglycerols but decrease the stimulation by insulin in 3T3-L1 adipocytes. Ceramides 15-24 insulin Homo sapiens 116-123 12532151-7 2003 However, C(2)-ceramide decreased the insulin-stimulated component of these signalling pathways and also glucose incorporation into triacylglycerol after 2 h. CONCLUSIONS: Cell-permeable ceramides can mimic some effects of TNFalpha in producing insulin resistance. Ceramides 186-195 insulin Homo sapiens 37-44 12532151-7 2003 However, C(2)-ceramide decreased the insulin-stimulated component of these signalling pathways and also glucose incorporation into triacylglycerol after 2 h. CONCLUSIONS: Cell-permeable ceramides can mimic some effects of TNFalpha in producing insulin resistance. Ceramides 186-195 insulin Homo sapiens 244-251 11872660-8 2002 In addition to downregulation of PDE3B, the antilipolytic action of insulin was decreased by ceramide treatment. Ceramides 93-101 insulin Homo sapiens 68-75 11872660-9 2002 These results, together with data from other studies on PDE3B and lipolysis in diabetic humans and animals, suggest a novel pathway by which ceramide induces insulin resistance. Ceramides 141-149 insulin Homo sapiens 158-165 11751589-0 2002 Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. Ceramides 0-8 insulin Homo sapiens 79-86 11751589-3 2002 In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. Ceramides 34-42 insulin Homo sapiens 73-80 11679435-8 2001 Our results indicate that ceramide produced by TNF-alpha induces insulin resistance in brown adipocytes by maintaining Akt in an inactive dephosphorylated state. Ceramides 26-34 insulin Homo sapiens 65-72 14560023-1 2003 Ceramide is generated in response to numerous stress-inducing stimuli and has been implicated in the regulation of diverse cellular responses, including cell death, differentiation, and insulin sensitivity. Ceramides 0-8 insulin Homo sapiens 186-193 14560023-2 2003 Recent evidence indicates that ceramide may regulate these responses by inhibiting the stimulus-mediated activation of protein kinase B (PKB), a key determinant of cell fate and insulin action. Ceramides 31-39 insulin Homo sapiens 178-185 14560023-10 2003 Since PKB confers a prosurvival signal and regulates numerous pathways in response to insulin, suppressing its activation by a PKCzeta-dependent process may be one mechanism by which ceramide promotes cell death and induces insulin resistance. Ceramides 183-191 insulin Homo sapiens 86-93 14560023-10 2003 Since PKB confers a prosurvival signal and regulates numerous pathways in response to insulin, suppressing its activation by a PKCzeta-dependent process may be one mechanism by which ceramide promotes cell death and induces insulin resistance. Ceramides 183-191 insulin Homo sapiens 224-231 12643176-4 2002 These impairments appear to be at least indirectly centered on the ability of mitochondria to oxidize fatty acids, possibly through mediation of lipid metabolite levels such as ceramide or diacylglycerol, which are known to directly attenuate insulin signaling. Ceramides 177-185 insulin Homo sapiens 243-250 11679435-0 2001 Ceramide mediates insulin resistance by tumor necrosis factor-alpha in brown adipocytes by maintaining Akt in an inactive dephosphorylated state. Ceramides 0-8 insulin Homo sapiens 18-25 11679435-3 2001 A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4. Ceramides 14-22 insulin Homo sapiens 65-72 11679435-3 2001 A short-chain ceramide analog, C2-ceramide, completely precluded insulin-stimulated glucose uptake and insulin-induced GLUT4 translocation to plasma membrane, as determined by Western blot or immunofluorescent localization of GLUT4. Ceramides 14-22 insulin Homo sapiens 103-110 11587538-0 2001 Inhibition of ceramide production reverses TNF-induced insulin resistance. Ceramides 14-22 insulin Homo sapiens 55-62 11587538-1 2001 Ceramide has been implicated as a mediator of insulin resistance induced by tumor necrosis factor-alpha (TNF) in adipocytes. Ceramides 0-8 insulin Homo sapiens 46-53 11587538-6 2001 These results suggest that TNF-independent increases in caveolar pools of ceramide are not sufficient to inhibit insulin signaling but that in conjunction with other TNF-dependent signals, caveolar pools of ceramide are a critical component for insulin resistance by TNF. Ceramides 207-215 insulin Homo sapiens 245-252 11523631-5 2001 In other experiments, the ability of C2 ceramide (Cer) to inhibit insulin action and induce IR was assessed as well as the phospholipase C inhibitor D609 to reverse IR induced by these TNF-alpha-like agents. Ceramides 50-53 insulin Homo sapiens 66-73 11270673-1 2001 AIMS/HYPOTHESIS: Increased cellular production of ceramide has been implicated in the pathogenesis of insulin resistance and in the impaired utilisation of glucose. Ceramides 50-58 insulin Homo sapiens 102-109 11270673-2 2001 In this study we have used L6 muscle cells to investigate the mechanism by which the short-chain ceramide analogue, C2-ceramide, promotes a loss in insulin sensitivity leading to a reduction in insulin stimulated glucose transport and glycogen synthesis. Ceramides 97-105 insulin Homo sapiens 148-155 11270673-4 2001 RESULTS: Incubation of L6 muscle cells with ceramide (100 micromol/l) for 2 h led to a complete loss of insulin-stimulated glucose transport and glycogen synthesis. Ceramides 44-52 insulin Homo sapiens 104-111 11900368-0 2001 Tumor necrosis factor-alpha, sphingomyelinase and ceramides activate tyrosine kinase, p21Ras and phosphatidylinositol 3-kinase: implications for glucose transport and insulin resistance. Ceramides 50-59 insulin Homo sapiens 167-174 11460570-5 2001 A key factor is seen to be accumulation of muscle long chain acyl CoAs, which could alter insulin action via several mechanisms including chronic activation of protein kinase C isoforms or ceramide accumulation. Ceramides 189-197 insulin Homo sapiens 90-97 11042022-2 2000 This study investigated the contribution of Akt and p70S6-kinase in insulin rescue from two different apoptotic triggers, serum deprivation and ceramide treatment. Ceramides 144-152 insulin Homo sapiens 68-75 9794783-8 1998 Signalling of the stress response through ceramide appears to play a role in the development of human diseases, including ischaemia/reperfusion injury, insulin resistance and diabetes, atherogenesis, septic shock and ovarian failure. Ceramides 42-50 insulin Homo sapiens 152-159 10842662-7 1999 Interestingly, soluble analogues of ceramide antagonize both insulin"s activation of Akt/PKB as well as its stimulation of glucose transport, consistent with a causal relationship between the two. Ceramides 36-44 insulin Homo sapiens 61-68 10419100-0 1999 Tumor necrosis factor-alpha and ceramides in insulin resistance. Ceramides 32-41 insulin Homo sapiens 45-52 10419100-10 1999 Our work provides further mechanisms whereby TNF-alpha and ceramides produce insulin resistance and decrease the effectiveness of insulin in stimulating glucose disposal from the blood. Ceramides 59-68 insulin Homo sapiens 77-84 10419100-10 1999 Our work provides further mechanisms whereby TNF-alpha and ceramides produce insulin resistance and decrease the effectiveness of insulin in stimulating glucose disposal from the blood. Ceramides 59-68 insulin Homo sapiens 130-137 9710629-9 1998 These studies demonstrate ceramide"s capacity to inhibit activation of Akt and imply that this is a mechanism of antagonism of insulin-dependent physiological events, such as the peripheral activation of glucose transport and the suppression of apoptosis. Ceramides 26-34 insulin Homo sapiens 127-134 8960353-8 1996 Tumor necrosis factor-alpha causes insulin resistance, which may be partly explained by ceramide production. Ceramides 88-96 insulin Homo sapiens 35-42 9710629-0 1998 Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Ceramides 100-108 insulin Homo sapiens 14-21 9710629-2 1998 Recently published reports indicate that ceramide levels are elevated in insulin-responsive tissues of diabetic animals and that agents which trigger ceramide production inhibit insulin signaling. Ceramides 41-49 insulin Homo sapiens 73-80 9710629-2 1998 Recently published reports indicate that ceramide levels are elevated in insulin-responsive tissues of diabetic animals and that agents which trigger ceramide production inhibit insulin signaling. Ceramides 41-49 insulin Homo sapiens 178-185 9710629-2 1998 Recently published reports indicate that ceramide levels are elevated in insulin-responsive tissues of diabetic animals and that agents which trigger ceramide production inhibit insulin signaling. Ceramides 150-158 insulin Homo sapiens 178-185 9710629-3 1998 In the present series of studies, the short-chain ceramide analog C2-ceramide inhibited insulin-stimulated glucose transport by approximately 50% in 3T3-L1 adipocytes, with similar reductions in hormone-stimulated translocation of the insulin-responsive glucose transporter (GLUT4) and insulin-responsive aminopeptidase. Ceramides 50-58 insulin Homo sapiens 88-95 9421370-0 1998 Effects of cell-permeable ceramides and tumor necrosis factor-alpha on insulin signaling and glucose uptake in 3T3-L1 adipocytes. Ceramides 26-35 insulin Homo sapiens 71-78 9421370-1 1998 Incubation of 3T3-L1 adipocytes with C2- and C6-ceramides (N-acetyl- and N-hexanoylsphingosines) but not dihydro-C2-ceramide increased 2-deoxyglucose uptake in the absence of insulin. Ceramides 48-57 insulin Homo sapiens 175-182 9421370-10 1998 Our work provides further mechanisms for the effects of TNF-alpha and ceramides in increasing non-insulin-dependent glucose uptake and decreasing insulin-stimulated uptake in vivo. Ceramides 70-79 insulin Homo sapiens 98-105 9421370-10 1998 Our work provides further mechanisms for the effects of TNF-alpha and ceramides in increasing non-insulin-dependent glucose uptake and decreasing insulin-stimulated uptake in vivo. Ceramides 70-79 insulin Homo sapiens 146-153 8870666-0 1996 Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes. Ceramides 39-47 insulin Homo sapiens 19-26 8960353-9 1996 Cell-permeable ceramides decrease insulin-stimulated glucose uptake in 3T3-L1 adipocytes after 2-24 h, whereas they stimulate basal glucose uptake. Ceramides 15-24 insulin Homo sapiens 34-41 33033923-11 2020 Five glycosylated ceramides were increased in insulin autoantibody (IAA) positive adolescent subjects compared to adolescent subjects without this autoantibody. Ceramides 18-27 insulin Homo sapiens 46-53 7607324-0 1995 Ceramide inhibits pancreatic beta-cell insulin production and mitogenesis and mimics the actions of interleukin-1 beta. Ceramides 0-8 insulin Homo sapiens 39-46 7607324-2 1995 The effects of endogenously generated and exogenously delivered ceramide on long-term insulin secretion and replication by pancreatic beta-cells were investigated, and compared to the effects of interleukin 1 beta (IL-1 beta). Ceramides 64-72 insulin Homo sapiens 86-93 7607324-3 1995 Generation of beta-cell ceramide by exogenous sphingomyelinase, or addition of cell-permeant ceramide analogs C2-ceramide and C6-ceramide, caused inhibitor effects on beta-cell insulin production and mitogenesis mimicing those evoked by IL-1 beta. Ceramides 24-32 insulin Homo sapiens 177-184 33815291-4 2021 A significant number of studies have described the involvement of ceramides and other sphingolipids in the inhibition of insulin-signaling pathway in both skeletal muscles and the liver. Ceramides 66-75 insulin Homo sapiens 121-128 34273578-4 2021 Indeed, excessive hypothalamic de novo ceramide synthesis have been shown to result in the establishment of central insulin resistance, endoplasmic reticulum stress and inflammation. Ceramides 39-47 insulin Homo sapiens 116-123 34962430-8 2022 Ceramides prevented insulin-induced phosphorylation of PKB and NDRG1, but not of Nedd4-2. Ceramides 0-9 insulin Homo sapiens 20-27 34962430-11 2022 Sphingosine 1-phosphate might protect Nedd4-2 against ceramide-induced insulin resistance. Ceramides 54-62 insulin Homo sapiens 71-78 34954721-4 2022 Ceramides, such as sphingolipids are also produced intracellularly and have signalling actions in regulating cell metabolism including effects on inflammation, and potentially have a mechanistic role in the development of insulin resistance. Ceramides 0-9 insulin Homo sapiens 222-229 34288516-4 2021 Counteracting the deleterious effects of high-fat diets (HFDs) rich in saturated fat either by inhibiting synthesis or by promoting degradation of ceramides mitigates insulin resistance and ectopic lipid accumulation (Meikle and Summers 2017). Ceramides 147-156 insulin Homo sapiens 167-174 34417267-0 2021 Surplus Ceramides: An Added Twist in the Tale of TREM2 and Insulin Resistance. Ceramides 8-17 insulin Homo sapiens 59-66 34257427-7 2021 Moreover, saturated fat raises IHTG more than polyunsaturated or monounsaturated fats, with adverse effects on insulin sensitivity, which are probably mediated in part by increased ceramide synthesis. Ceramides 181-189 insulin Homo sapiens 111-118 34285405-5 2021 These extracellular factors perturb the intracellular concentration of a range of intermediates, including ceramide and other lipids, leading to defects in responsiveness of cells to insulin. Ceramides 107-115 insulin Homo sapiens 183-190 34069652-7 2021 This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. Ceramides 26-35 insulin Homo sapiens 176-183 34197026-3 2021 Two approaches for rendering the SWCNT sensors for insulin are compared, using surface functionalization with either a natural insulin aptamer with known affinity to insulin, or a synthetic lipid-poly(ethylene glycol) (PEG) (C16 -PEG(2000Da)-Ceramide), both of which show a modulation of the emitted fluorescence in response to insulin. Ceramides 242-250 insulin Homo sapiens 51-58 34197026-3 2021 Two approaches for rendering the SWCNT sensors for insulin are compared, using surface functionalization with either a natural insulin aptamer with known affinity to insulin, or a synthetic lipid-poly(ethylene glycol) (PEG) (C16 -PEG(2000Da)-Ceramide), both of which show a modulation of the emitted fluorescence in response to insulin. Ceramides 242-250 insulin Homo sapiens 328-335 34197026-4 2021 Although the PEGylated-lipid has no prior affinity to insulin, the response of C16 -PEG(2000Da)-Ceramide-SWCNTs to insulin is more stable and reproducible compared to the insulin aptamer-SWCNTs. Ceramides 96-104 insulin Homo sapiens 54-61 34197026-4 2021 Although the PEGylated-lipid has no prior affinity to insulin, the response of C16 -PEG(2000Da)-Ceramide-SWCNTs to insulin is more stable and reproducible compared to the insulin aptamer-SWCNTs. Ceramides 96-104 insulin Homo sapiens 115-122 35584813-4 2022 Sphingolipids such as ceramides are among the most deleterious and bioactive metabolites that accrue, as they participate in selective insulin resistance, dyslipidemia, oxidative stress and apoptosis. Ceramides 22-31 insulin Homo sapiens 135-142 35508667-1 2022 Ectopic ceramide accumulation in insulin-responsive tissues contributes to the development of obesity and impairs insulin sensitivity. Ceramides 8-16 insulin Homo sapiens 33-40 35470585-5 2022 Within-tissue analysis showed higher mean levels of ceramide species linked to insulin resistance, such as Cer(d18:1/18:0) and Cer(d18:1/16:0), in visceral tissue of prediabetic/diabetic patients compared with nondiabetic subjects and higher content of Cer(d18:1/14:0) in subcutaneous tissue of insulin-resistant female patients compared with prediabetic/diabetic males. Ceramides 52-60 insulin Homo sapiens 79-86 35422650-0 2022 alpha-Lipoic Acid Reduces Ceramide Synthesis and Neuroinflammation in the Hypothalamus of Insulin-Resistant Rats, While in the Cerebral Cortex Diminishes the beta-Amyloid Accumulation. Ceramides 26-34 insulin Homo sapiens 90-97 35061523-3 2022 Rather, insulin resistance is caused, at least in part, by the presence of high concentrations of harmful lipid metabolites, such as diacylglycerols and ceramides in muscle. Ceramides 153-162 insulin Homo sapiens 8-15 35470585-5 2022 Within-tissue analysis showed higher mean levels of ceramide species linked to insulin resistance, such as Cer(d18:1/18:0) and Cer(d18:1/16:0), in visceral tissue of prediabetic/diabetic patients compared with nondiabetic subjects and higher content of Cer(d18:1/14:0) in subcutaneous tissue of insulin-resistant female patients compared with prediabetic/diabetic males. Ceramides 52-60 insulin Homo sapiens 295-302 35470585-6 2022 Statistically significant differences in mean levels of ceramide species between insulin-resistant African American and insulin-resistant Caucasian patients were not evident in visceral or subcutaneous tissue. Ceramides 56-64 insulin Homo sapiens 81-88 35470585-6 2022 Statistically significant differences in mean levels of ceramide species between insulin-resistant African American and insulin-resistant Caucasian patients were not evident in visceral or subcutaneous tissue. Ceramides 56-64 insulin Homo sapiens 120-127 35470585-8 2022 Knowledge of the accumulated ceramides/dihydroceramides may reflect on the prelipolytic state that leads the lipotoxic phase of insulin resistance and may shed light on the predisposition to insulin resistance by gender. Ceramides 29-38 insulin Homo sapiens 128-135 35470585-8 2022 Knowledge of the accumulated ceramides/dihydroceramides may reflect on the prelipolytic state that leads the lipotoxic phase of insulin resistance and may shed light on the predisposition to insulin resistance by gender. Ceramides 29-38 insulin Homo sapiens 191-198 35406045-0 2022 Effects of Isocaloric Fructose Restriction on Ceramide Levels in Children with Obesity and Cardiometabolic Risk: Relation to Hepatic De Novo Lipogenesis and Insulin Sensitivity. Ceramides 46-54 insulin Homo sapiens 157-164 35406045-3 2022 Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. Ceramides 0-9 insulin Homo sapiens 96-103 35406045-8 2022 Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Ceramides 23-31 insulin Homo sapiens 77-84 35406045-10 2022 These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR. Ceramides 27-36 insulin Homo sapiens 117-124 35406045-10 2022 These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR. Ceramides 27-36 insulin Homo sapiens 198-205 35066602-10 2022 Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. Ceramides 25-33 insulin Homo sapiens 104-111 35066602-10 2022 Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. Ceramides 25-33 insulin Homo sapiens 190-197 35066602-10 2022 Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. Ceramides 159-168 insulin Homo sapiens 104-111 35066602-10 2022 Positive associations of ceramide C22:0/C24:0 and their precursors with homeostasis model assessment of insulin resistance suggested that the synthesis of the ceramides might be involved in insulin resistance. Ceramides 159-168 insulin Homo sapiens 190-197 35184720-4 2022 In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. Ceramides 20-29 insulin Homo sapiens 136-143 35184720-5 2022 This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. Ceramides 57-66 insulin Homo sapiens 128-135 35111371-1 2022 Ceramide is a core molecule of sphingolipid metabolism that causes selective insulin resistance and dyslipidemia. Ceramides 0-8 insulin Homo sapiens 77-84 33738905-1 2021 Sphingolipids, in particular ceramides, play vital role in pathophysiological processes linked to metabolic syndrome, with implications in the development of insulin resistance, pancreatic ss-cell dysfunction, type 2 diabetes, atherosclerosis, inflammation, nonalcoholic steatohepatitis, and cancer. Ceramides 29-38 insulin Homo sapiens 158-165 35054078-8 2022 Sphingolipids are known to be a modulator of insulin resistance, and our results indicate that ceramide measurements in early pregnancy may help with GDM screening. Ceramides 95-103 insulin Homo sapiens 45-52 33630410-4 2021 Accumulation of these ceramides is associated with insulin resistance, de novo lipogenesis, and inflammation1 , thus increasing the risk of cardiometabolic diseases such as type 2 diabetes (T2D) and atherosclerosis. Ceramides 22-31 insulin Homo sapiens 51-58 33504931-9 2021 In addition, a network of 89 metabolites, primarily phosphatidylcholines, plasmalogens, sphingomyelins, and ceramides showed consistent negative correlations with insulin at visit 1 and post-challenge glucose at visit 2, while positive correlation with adiponectin at visit 2. Ceramides 108-117 insulin Homo sapiens 163-170 34004484-3 2021 Recent studies have highlighted circulating ceramides as novel biomarkers of coronary artery disease, type-2 diabetes and insulin resistance. Ceramides 44-53 insulin Homo sapiens 122-129 33158378-3 2021 Among the numerous lipid subtypes that accumulate, sphingolipids such as ceramides are particularly impactful, as they elicit the selective insulin resistance, dyslipidemia, and ultimately cell death that underlie nearly all metabolic disorders. Ceramides 73-82 insulin Homo sapiens 140-147 33296380-1 2020 BACKGROUND: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, beta-cell dysfunction, and inflammation, but human studies are limited. Ceramides 76-85 insulin Homo sapiens 157-164 33268241-2 2021 Lipids have long been recognized as contributors to the pathogenesis and pathophysiology of DM and its complications, but recent discoveries have highlighted ceramides, a class of bioactive sphingolipids with cell signaling and second messenger capabilities, as particularly important contributors to insulin resistance and the underlying mechanisms of DM complications. Ceramides 158-167 insulin Homo sapiens 301-308 33268241-3 2021 Besides their association with insulin resistance and pathophysiology of type 2 diabetes, evidence is emerging that certain species of ceramides are mediators of cellular mechanisms involved in the initiation and progression of microvascular and macrovascular complications of DM. Ceramides 135-144 insulin Homo sapiens 31-38 33492226-0 2021 [Is obesity-induced insulin resistance mediated by ceramide C18:0 synthesis de novo in skeletal muscles]. Ceramides 51-59 insulin Homo sapiens 20-27 32766878-12 2020 Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways. Ceramides 0-9 insulin Homo sapiens 58-65 33058843-2 2020 Elevated plasma concentrations of ceramides are associated with multiple risk factors of atherosclerotic cardiovascular diseases and comorbidities including e.g. obesity, insulin resistance and diabetes mellitus. Ceramides 34-43 insulin Homo sapiens 171-178 33219119-0 2020 Role of ceramide-to-dihydroceramide ratios for insulin resistance and non-alcoholic fatty liver disease in humans. Ceramides 8-16 insulin Homo sapiens 47-54 32668665-4 2020 Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic beta cell death. Ceramides 0-8 insulin Homo sapiens 46-53 32641420-2 2020 Inhibition of ceramide biosynthesis has been shown in model systems to antagonize obesity and improve insulin sensitivity. Ceramides 14-22 insulin Homo sapiens 102-109 32849276-3 2020 Recent studies have demonstrated that the acyl-chain is an important determinant of ceramide function, such that a small subset of ceramides (e.g., those containing the C16 or C18 acyl-chain) alter metabolism by inhibiting insulin signaling or inducing mitochondrial fragmentation. Ceramides 84-92 insulin Homo sapiens 223-230 32849276-3 2020 Recent studies have demonstrated that the acyl-chain is an important determinant of ceramide function, such that a small subset of ceramides (e.g., those containing the C16 or C18 acyl-chain) alter metabolism by inhibiting insulin signaling or inducing mitochondrial fragmentation. Ceramides 131-140 insulin Homo sapiens 223-230 32430917-0 2020 Plasma Ceramides and Triglycerides Are Elevated during Pregnancy in Association with Markers of Insulin Resistance in Hutterite Women. Ceramides 7-16 insulin Homo sapiens 96-103 32430917-2 2020 Although ceramides can cause insulin resistance in mammals, their potential roles during pregnancy and lactation are unknown. Ceramides 9-18 insulin Homo sapiens 29-36 32430917-3 2020 We hypothesized that changes in lipids like ceramide and triglycerides could occur across different reproductive states and relate to insulin resistance. Ceramides 44-52 insulin Homo sapiens 134-141 32430917-9 2020 Our data support the possibility that ceramides contribute to the development of insulin resistance during pregnancy, and reveal distinct lipid signatures associated with pregnancy and lactation. Ceramides 38-47 insulin Homo sapiens 81-88 32636806-7 2020 Notably, recent experimental studies have strongly implicated ceramides in the development of numerous metabolic diseases such as insulin resistance, diabetes, cardiomyopathy, hepatic-steatosis, and atherosclerosis. Ceramides 62-71 insulin Homo sapiens 130-137 32455838-4 2020 Two separate but somewhat overlapping models-the diacylglycerol (DAG) model and the ceramide model-have emerged to explain the development of insulin resistance. Ceramides 84-92 insulin Homo sapiens 142-149 32392908-4 2020 Accumulation of ceramides alters substrate utilization from glucose to lipids, activates triglyceride storage, and results in the development of both insulin resistance and hepatosteatosis, increasing the likelihood of major metabolic diseases. Ceramides 16-25 insulin Homo sapiens 150-157 32455838-5 2020 Studies have shown that lipid deposition in tissues such as muscle and liver inhibit insulin signaling via the toxic molecules DAG and ceramide. Ceramides 135-143 insulin Homo sapiens 85-92 32455838-7 2020 Ceramides are sphingolipids with variable acyl group chain length and activate protein phosphatase 2A that dephosphorylates Akt to block insulin signaling. Ceramides 0-9 insulin Homo sapiens 137-144 32144130-7 2020 As placental ceramide induces mitochondrial fission in pre-eclampsia, we also examined ceramide content in GDM and control placentae and observed a reduction in placental ceramide enrichment in GDM, likely due to an insulin-dependent increase in ceramide-degrading ASAH1 expression. Ceramides 13-21 insulin Homo sapiens 216-223 32424203-2 2020 Ceramides, a type of sphingolipid (SL), have been implicated in the development of a range of metabolic disorders from insulin resistance (IR) to hepatic steatosis. Ceramides 0-9 insulin Homo sapiens 119-126 32452372-0 2020 [Ceramides, crucial actors in the development of insulin resistance and type 2 diabetes]. Ceramides 1-10 insulin Homo sapiens 49-56 32452372-6 2020 Numerous studies have shown that ceramides are among the most active lipid second messengers to inhibit insulin signalling. Ceramides 33-42 insulin Homo sapiens 104-111 32452372-7 2020 This review describes the major role played by ceramides in the development of insulin resistance in peripheral tissues. Ceramides 47-56 insulin Homo sapiens 79-86 31899812-0 2020 Ceramides - a cause of insulin resistance in NAFLD in both murine models and humans. Ceramides 0-9 insulin Homo sapiens 23-30 30803019-3 2020 In the present review, we consider the available evidence on the possible roles of ceramides in diabetes mellitus and introduce eight different molecular mechanisms mediating the diabetogenic action of ceramides, categorized into those predominantly related to insulin resistance vs those mainly implicated in beta-cell dysfunction. Ceramides 202-211 insulin Homo sapiens 261-268 30803019-2 2020 Ceramides are primarily recognized as lipid bilayer building blocks, but recent work has shown that these endogenous molecules are important intracellular signalling mediators and may exert some diabetogenic effects via molecular pathways involved in insulin resistance, beta-cell apoptosis and inflammation. Ceramides 0-9 insulin Homo sapiens 251-258 32098447-2 2020 A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Ceramides 46-55 insulin Homo sapiens 111-118 32098447-2 2020 A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Ceramides 46-55 insulin Homo sapiens 137-144 32098447-3 2020 Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Ceramides 41-50 insulin Homo sapiens 64-71 31842461-0 2019 Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients. Ceramides 0-8 insulin Homo sapiens 47-54 32489964-1 2020 Objective: Total ceramide concentrations are linked with increased insulin resistance and cardiac dysfunction. Ceramides 17-25 insulin Homo sapiens 67-74 32821721-4 2020 When prolonged, these ceramide actions cause insulin resistance and hepatic steatosis, 2 of the underlying drivers of cardiometabolic diseases. Ceramides 22-30 insulin Homo sapiens 45-52 32821721-5 2020 Herein the author discusses the mechanisms linking ceramides to the development of insulin resistance, hepatosteatosis and resultant cardiometabolic disorders. Ceramides 51-60 insulin Homo sapiens 83-90 31842461-3 2019 We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. Ceramides 96-104 insulin Homo sapiens 50-57 31842461-14 2019 These data indicate ceramide contribution to the induction of hepatic insulin resistance. Ceramides 20-28 insulin Homo sapiens 70-77 31605240-6 2019 RESULTS: Confirming the link to deteriorated glucose homeostasis, serum ceramides were positively correlated with fasting glucose, but inversely correlated with fasting and OGTT-derived measures of insulin sensitivity and beta-cell function. Ceramides 72-81 insulin Homo sapiens 198-205 31647034-7 2019 RESULTS: Immunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Ceramides 47-56 insulin Homo sapiens 102-109 31647034-14 2019 Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration. Ceramides 30-38 insulin Homo sapiens 88-95 31496996-0 2019 The Role of Ceramides in Insulin Resistance. Ceramides 12-21 insulin Homo sapiens 25-32 30071259-7 2019 An unbalanced ratio between ceramides and terminal metabolic products in the liver and plasma promotes weight gain, inflammation, and insulin resistance. Ceramides 28-37 insulin Homo sapiens 134-141 31342535-1 2019 Ceramides (CER) are biologically active sphingolipid precursors that are mechanistically linked to several pathogenic states including cancer, insulin resistance, and neurodegeneration. Ceramides 0-9 insulin Homo sapiens 143-150 31342535-1 2019 Ceramides (CER) are biologically active sphingolipid precursors that are mechanistically linked to several pathogenic states including cancer, insulin resistance, and neurodegeneration. Ceramides 11-14 insulin Homo sapiens 143-150 31137828-0 2019 Sulforaphane Prevents Hepatic Insulin Resistance by Blocking Serine Palmitoyltransferase 3-Mediated Ceramide Biosynthesis. Ceramides 100-108 insulin Homo sapiens 30-37 30592185-2 2018 We investigated if insulin-stimulated activation of Rac1 (i.e., Rac1-GTP binding) is impaired by accumulation of diacylglycerols (DAG) and ceramides in cultured muscle cells. Ceramides 139-148 insulin Homo sapiens 19-26 30871020-1 2019 Ceramide and diacylglycerol are linked to insulin resistance in rodents, but in humans the data are inconsistent. Ceramides 0-8 insulin Homo sapiens 42-49 30871020-11 2019 This study highlights an increased content of saturated ceramides in aging which could be speculated to influence insulin sensitivity. Ceramides 56-65 insulin Homo sapiens 114-121 30678043-9 2019 Ceramides, which are synthetized de novo from saturated FA like palmitate, have been demonstrated to play a critical role in the deterioration of insulin sensitivity in muscle cells. Ceramides 0-9 insulin Homo sapiens 146-153 30678043-10 2019 This review describes the latest progress involving ceramides as major players in the development of muscle insulin-resistance through the targeting of selective actors of the insulin signaling pathway. Ceramides 52-61 insulin Homo sapiens 108-115 30678043-10 2019 This review describes the latest progress involving ceramides as major players in the development of muscle insulin-resistance through the targeting of selective actors of the insulin signaling pathway. Ceramides 52-61 insulin Homo sapiens 176-183 31562630-6 2019 In addition, we highlight the main studies describing effects of ceramides in inflammation, specifically in various inflammatory settings including insulin resistance, graft-versus-host disease, immune suppression in cancer, multiple sclerosis, and inflammatory bowel disease. Ceramides 65-74 insulin Homo sapiens 148-155 30159588-0 2018 Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study. Ceramides 19-28 insulin Homo sapiens 52-59 30159588-1 2018 AIMS/HYPOTHESIS: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. Ceramides 17-26 insulin Homo sapiens 64-71 30159588-2 2018 We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. Ceramides 28-37 insulin Homo sapiens 86-93 30159588-13 2018 The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation. Ceramides 12-21 insulin Homo sapiens 98-105 30208901-12 2018 Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Ceramides 81-90 insulin Homo sapiens 95-102 30208901-16 2018 CONCLUSION: Elevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease. Ceramides 21-29 insulin Homo sapiens 112-119 29546476-1 2018 AIMS/HYPOTHESIS: Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Ceramides 17-25 insulin Homo sapiens 67-74 29509438-2 2018 Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that are involved in cardiometabolic disease. Ceramides 0-9 insulin Homo sapiens 98-105 29588286-1 2018 Experimental studies suggest ceramides may play a role in insulin resistance. Ceramides 29-38 insulin Homo sapiens 58-65 29588286-2 2018 However, the relationships of circulating ceramides and related sphingolipids with plasma insulin have been underexplored in humans. Ceramides 42-51 insulin Homo sapiens 90-97 29588286-5 2018 Among the 2,086 participants without diabetes, higher levels of plasma ceramides carrying the fatty acids 16:0 (16 carbons, 0 double bond), 18:0, 20:0, or 22:0 were associated with higher plasma insulin and higher HOMA-IR at baseline and at follow-up an average of 5.4 years later. Ceramides 71-80 insulin Homo sapiens 195-202 29588286-6 2018 For example, a twofold higher baseline concentration of ceramide 16:0 was associated with 14% higher baseline insulin (P < 0.0001). Ceramides 56-64 insulin Homo sapiens 110-117 29751643-7 2018 Thus, the lean-seafood diet decreased circulating isoleucine and valine levels, whereas the non-seafood diet elevated the levels of certain ceramides, metabolites that are associated with insulin-resistance. Ceramides 140-149 insulin Homo sapiens 188-195 29359558-3 2018 We find that a C16-PEG(2000 Da)-ceramide causes a 62% fluorescent intensity decrease of the (10,2) chirality nanotube in the presence of 20 mug/mL insulin. Ceramides 32-40 insulin Homo sapiens 147-154 29359558-4 2018 The insulin protein has no prior affinity toward the C16-PEG(2000 Da)-ceramide molecules in free solution, verified by isothermal titration calorimetry, and the interaction occurs only upon their adsorption onto the single-walled carbon nanotube scaffolds. Ceramides 70-78 insulin Homo sapiens 4-11 29415895-7 2018 Sarcolemmal ceramides were inversely related to insulin sensitivity, with a significant relationship found for the C18:0 species. Ceramides 12-21 insulin Homo sapiens 48-55 29415895-9 2018 In the mitochondrial/ER and nuclear fractions, 1,2-DAGs were positively related to, while ceramides were inversely related to, insulin sensitivity. Ceramides 90-99 insulin Homo sapiens 127-134 28970356-6 2018 The increases in SS C24 ceramides were negatively related to parameters of insulin resistance. Ceramides 24-33 insulin Homo sapiens 75-82 30060808-5 2018 Insulin sensitivity, de novo lipogenesis, and the resulting lipotoxicity, fibrosis, and angiogenesis are all seemingly regulated in a manner that involves either ceramide and/or sphingosine-1-phosphate. Ceramides 162-170 insulin Homo sapiens 0-7 28483801-4 2017 We found that HOMA of insulin resistance, plasma insulin, and triglyceride concentrations were positively correlated with SS C16:0 and C18:1 ceramide, but not SS C14:0-Cer, C20:0-Cer, C24:0-Cer, and C24:1-Cer concentrations; IMF ceramide concentrations were not correlated with any metabolic parameters. Ceramides 141-149 insulin Homo sapiens 22-29 29660940-11 2018 Ceramide is a pro-apoptotic lipid, and heavily implicated as a driver of insulin resistance in metabolic tissues. Ceramides 0-8 insulin Homo sapiens 73-80 28483801-4 2017 We found that HOMA of insulin resistance, plasma insulin, and triglyceride concentrations were positively correlated with SS C16:0 and C18:1 ceramide, but not SS C14:0-Cer, C20:0-Cer, C24:0-Cer, and C24:1-Cer concentrations; IMF ceramide concentrations were not correlated with any metabolic parameters. Ceramides 141-149 insulin Homo sapiens 49-56 28483801-6 2017 Plasma insulin concentrations correlated positively with the fractional contribution of plasma palmitate to SS 16:0 ceramide. Ceramides 116-124 insulin Homo sapiens 7-14 28483801-8 2017 We conclude that skeletal muscle SS ceramides, especially C16 to C18 chain lengths and the de novo synthesis of intramyocellular ceramide from plasma palmitate are associated with markers of insulin resistance. Ceramides 36-45 insulin Homo sapiens 191-198 28483801-8 2017 We conclude that skeletal muscle SS ceramides, especially C16 to C18 chain lengths and the de novo synthesis of intramyocellular ceramide from plasma palmitate are associated with markers of insulin resistance. Ceramides 36-44 insulin Homo sapiens 191-198 28714882-2 2017 Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Ceramides 143-151 insulin Homo sapiens 33-40 29069751-0 2017 A peptide antagonist of Prep1-p160 interaction improves ceramide-induced insulin resistance in skeletal muscle cells. Ceramides 56-64 insulin Homo sapiens 73-80 28551355-0 2017 Roles of Diacylglycerols and Ceramides in Hepatic Insulin Resistance. Ceramides 29-38 insulin Homo sapiens 50-57 29069751-9 2017 All these findings suggest that disruption of the Prep1/p160 molecular interaction enhances insulin sensitivity impaired by ceramides in skeletal muscle cells and indicate this complex as an important target for type 2 diabetes. Ceramides 124-133 insulin Homo sapiens 92-99 29069751-4 2017 In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. Ceramides 28-37 insulin Homo sapiens 78-85 27940403-1 2017 BACKGROUND AND AIMS: Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Ceramides 52-61 insulin Homo sapiens 100-107 27940403-1 2017 BACKGROUND AND AIMS: Plasma sphingolipids including ceramides, and gangliosides are associated with insulin resistance (IR) through effects on insulin signalling and glucose metabolism. Ceramides 52-61 insulin Homo sapiens 143-150 27173510-0 2016 Compounds of the sphingomyelin-ceramide-glycosphingolipid pathways as secondary messenger molecules: new targets for novel therapies for fatty liver disease and insulin resistance. Ceramides 31-39 insulin Homo sapiens 161-168 27765765-1 2016 OBJECTIVE: Ceramides are molecular lipids implicated in apoptosis, inflammation, obesity, and insulin resistance. Ceramides 11-20 insulin Homo sapiens 94-101 27682164-0 2016 Role of Ceramide in Apoptosis and Development of Insulin Resistance. Ceramides 8-16 insulin Homo sapiens 49-56 27682164-3 2016 One of the main predispositions for the development of insulin resistance and diabetes is obesity, which is associated with ectopic fat deposition and significant increase in intracellular concentrations of cytotoxic ceramides. Ceramides 217-226 insulin Homo sapiens 55-62 27682164-4 2016 A possible approach to the restoration of tissue sensitivity to insulin in type 2 diabetes based on selective reduction of the content of cytotoxic ceramides is discussed. Ceramides 148-157 insulin Homo sapiens 64-71 27382035-6 2016 Because a reduction in skeletal muscle ceramide levels is frequently associated with improvements in insulin sensitivity in humans, the beneficial findings reported for reducing ceramides in preclinical studies may have clinical application in humans. Ceramides 39-47 insulin Homo sapiens 101-108 27255710-0 2016 Short Term Palmitate Supply Impairs Intestinal Insulin Signaling via Ceramide Production. Ceramides 69-77 insulin Homo sapiens 47-54 27255710-6 2016 We show that palmitic acid or palm oil increases ceramide production in intestinal cells and that treatment with a ceramide analogue partially reproduces the effects of palmitic acid on insulin signaling. Ceramides 115-123 insulin Homo sapiens 186-193 27255710-7 2016 In Caco-2/TC7 enterocytes, ceramide effects on insulin-dependent AKT phosphorylation are mediated by protein kinase C but not by protein phosphatase 2A. Ceramides 27-35 insulin Homo sapiens 47-54 27255710-8 2016 Finally, inhibiting de novo ceramide synthesis improves the response of palmitic acid-treated Caco-2/TC7 enterocytes to insulin. Ceramides 28-36 insulin Homo sapiens 120-127 26996141-0 2016 CrossTalk proposal: Intramyocellular ceramide accumulation does modulate insulin resistance. Ceramides 37-45 insulin Homo sapiens 73-80 27173510-1 2016 The compounds of sphingomyelin-ceramide-glycosphingolipid pathways have been studied as potential secondary messenger molecules in various systems, along with liver function and insulin resistance. Ceramides 31-39 insulin Homo sapiens 178-185 26739815-8 2016 CONCLUSIONS/INTERPRETATION: These data suggest ceramide and other sphingolipids containing stearate (18:0) are uniquely related to insulin resistance in skeletal muscle. Ceramides 47-55 insulin Homo sapiens 131-138 26780287-0 2016 Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. Ceramides 8-17 insulin Homo sapiens 43-50 26780287-1 2016 BACKGROUND & AIMS: Recent data in mice have identified de novo ceramide synthesis as the key mediator of hepatic insulin resistance (IR) that in humans characterizes increases in liver fat due to IR ("Metabolic NAFLD" but not that due to the I148M gene variant in PNPLA3 ("PNPLA3 NAFLD"). Ceramides 67-75 insulin Homo sapiens 117-124 26739815-1 2016 AIMS/HYPOTHESES: Ceramides and other sphingolipids comprise a family of lipid molecules that accumulate in skeletal muscle and promote insulin resistance. Ceramides 17-26 insulin Homo sapiens 135-142 26739815-9 2016 Recovery from an exercise bout decreased muscle ceramide concentration; this may represent a mechanism promoting the insulin-sensitising effects of acute exercise. Ceramides 48-56 insulin Homo sapiens 117-124 27777958-1 2016 Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. Ceramides 0-8 insulin Homo sapiens 72-79 26698173-0 2016 Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE. Ceramides 20-28 insulin Homo sapiens 36-43 26698173-6 2016 Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. Ceramides 52-60 insulin Homo sapiens 197-204 26698173-6 2016 Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. Ceramides 89-97 insulin Homo sapiens 197-204 26698173-10 2016 Together, in the long term, our results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). Ceramides 50-58 insulin Homo sapiens 94-101 26698173-11 2016 PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells. Ceramides 55-63 insulin Homo sapiens 111-118 26682540-0 2015 Insulin treatment increases myocardial ceramide accumulation and disrupts cardiometabolic function. Ceramides 39-47 insulin Homo sapiens 0-7 26682540-3 2015 Considering type 2 diabetics treated with insulin are more likely to suffer from heart complications, we sought to determine the specific effect of insulin on ceramide-dependent cardiometabolic risk factors, including insulin resistance and altered heart mitochondrial physiology. Ceramides 159-167 insulin Homo sapiens 148-155 26682540-3 2015 Considering type 2 diabetics treated with insulin are more likely to suffer from heart complications, we sought to determine the specific effect of insulin on ceramide-dependent cardiometabolic risk factors, including insulin resistance and altered heart mitochondrial physiology. Ceramides 159-167 insulin Homo sapiens 148-155 26682540-4 2015 METHODS: H9c2 cardiomyocytes and adult mice were treated with insulin with or without myriocin to inhibit ceramide biosynthesis. Ceramides 106-114 insulin Homo sapiens 62-69 26682540-10 2015 Second, they identify ceramide as a possible mediator of insulin-related heart disorders. Ceramides 22-30 insulin Homo sapiens 57-64 25966363-10 2015 CONCLUSIONS: Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. Ceramides 117-125 insulin Homo sapiens 188-195 25959529-1 2015 BACKGROUND: Metabolic syndrome (MetS) appears closely linked with ceramide accumulation, inducing insulin resistance and toxicity to multiple cell types. Ceramides 66-74 insulin Homo sapiens 98-105 25959529-2 2015 Animal studies demonstrate that thiazolidinediones (TZDs) reduce ceramide concentrations in plasma and skeletal muscle and support lowering of ceramide levels as a potential mediator of TZDs" mechanism of action in reducing insulin resistance; however, studies in humans have yet to be reported. Ceramides 143-151 insulin Homo sapiens 224-231 26022371-12 2015 Taken together, our data demonstrate that Abeta42 expression and ceramide-induced insulin resistance synergistically interact to exacerbate mitochondrial damage and that therapeutic efforts to reduce insulin resistance could lessen failures of energy production and mitochondrial dynamics. Ceramides 65-73 insulin Homo sapiens 82-89 26115843-4 2015 We found that both ceramide analogs D- and L-PDMP (1-phenyl 2-decanoylamino-3-morpholino-1-propanol), which have opposite effects on ganglioside synthesis, selectively inhibited GSK3beta via Ser9 phosphorylation independently of the upstream insulin/Akt pathway. Ceramides 19-27 insulin Homo sapiens 242-249 26126684-1 2015 Ceramides and sphingolipids are a family of lipid molecules that circulate in serum and accumulate in skeletal muscle, promoting insulin resistance. Ceramides 0-9 insulin Homo sapiens 129-136 26126684-2 2015 Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species. Ceramides 7-15 insulin Homo sapiens 51-58 26126684-2 2015 Plasma ceramide and dihydroceramide are related to insulin resistance, yet less is known regarding other ceramide and sphingolipid species. Ceramides 27-35 insulin Homo sapiens 51-58 25966363-0 2015 Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes. Ceramides 87-95 insulin Homo sapiens 9-16 25966363-9 2015 Decreases in total (r = -0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Ceramides 74-82 insulin Homo sapiens 131-138 25966363-10 2015 CONCLUSIONS: Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. Ceramides 13-22 insulin Homo sapiens 79-86 26412155-2 2015 Of the myriad lipids that accrue under these conditions, sphingolipids such as ceramide or its metabolites are amongst the most deleterious because they disrupt insulin sensitivity, pancreatic beta cell function, vascular reactivity, and mitochondrial metabolism. Ceramides 79-87 insulin Homo sapiens 161-168 26412155-3 2015 Remarkably, inhibiting ceramide biosynthesis or catalyzing ceramide degradation in rodents ameliorates many metabolic disorders including diabetes, cardiomyopathy, insulin resistance, atherosclerosis, and steatohepatitis. Ceramides 23-31 insulin Homo sapiens 164-171 26022371-0 2015 Synergistic effects of beta-amyloid and ceramide-induced insulin resistance on mitochondrial metabolism in neuronal cells. Ceramides 40-48 insulin Homo sapiens 57-64 26022371-3 2015 We investigated the additive and synergistic effects of intracellular Abeta42 and ceramide-induced insulin resistance on mitochondrial metabolism in SH-SY5Y and Neuro-2a cells. Ceramides 82-90 insulin Homo sapiens 99-106 26022371-4 2015 In our model, mitochondria take-up Abeta42 expressed through viral-mediated transfection and exposure of the same cells to ceramide produces resistance to insulin signaling. Ceramides 123-131 insulin Homo sapiens 155-162 25367746-3 2015 In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Ceramides 112-120 insulin Homo sapiens 61-68 25367746-3 2015 In skeletal muscle, increased ectopic adiposity is linked to insulin resistance through lipid mediators such as ceramide or DAG, inhibiting the insulin receptor signalling pathway. Ceramides 112-120 insulin Homo sapiens 144-151 25367746-8 2015 Saturated fatty acids can be regarded as the most detrimental of FFA, being capable of inducing insulin resistance and inflammation through lipid mediators such as ceramide, which can increase risk of developing atherosclerosis. Ceramides 164-172 insulin Homo sapiens 96-103 24606127-0 2014 Adiponectin inhibits insulin function in primary trophoblasts by PPARalpha-mediated ceramide synthesis. Ceramides 84-92 insulin Homo sapiens 21-28 26962194-15 2015 CONCLUSIONS: A healthy Nordic diet transiently modified the plasma lipidomic profile, specifically by increasing the concentrations of antioxidative plasmalogens and decreasing insulin resistance-inducing ceramides. Ceramides 205-214 insulin Homo sapiens 177-184 26488284-9 2015 CONCLUSION: Palmitate-induced alteration in the stoichiometric ratio of mitochondrial CPT isoforms leads to incomplete FAO and enhanced cytosolic ceramide accumulation that lead to insulin resistance. Ceramides 146-154 insulin Homo sapiens 181-188 26488284-10 2015 Fenofibrate ameliorated insulin resistance by restoring the altered stoichiometry by upregulating CPT2 and preventing, cytoplasmic ceramide accumulation. Ceramides 131-139 insulin Homo sapiens 24-31 25814122-9 2015 A possible means of counteracting ceramide action would be to prevent the accumulation of the specific ceramide species involved in both insulin resistance and beta-cell apoptosis/dysfunction. Ceramides 34-42 insulin Homo sapiens 137-144 25814122-9 2015 A possible means of counteracting ceramide action would be to prevent the accumulation of the specific ceramide species involved in both insulin resistance and beta-cell apoptosis/dysfunction. Ceramides 103-111 insulin Homo sapiens 137-144 26380311-0 2015 Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance. Ceramides 14-22 insulin Homo sapiens 83-90 25058613-0 2014 Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight. Ceramides 41-49 insulin Homo sapiens 55-62 25058613-1 2014 Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Ceramides 0-9 insulin Homo sapiens 31-38 25058613-1 2014 Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Ceramides 0-9 insulin Homo sapiens 148-155 25058613-7 2014 In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Ceramides 52-60 insulin Homo sapiens 107-114 25058613-8 2014 Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies. Ceramides 178-186 insulin Homo sapiens 145-152 24936246-0 2014 Defect of insulin signal in peripheral tissues: Important role of ceramide. Ceramides 66-74 insulin Homo sapiens 10-17 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-38 insulin Homo sapiens 104-111 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-38 insulin Homo sapiens 225-232 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-38 insulin Homo sapiens 225-232 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-37 insulin Homo sapiens 104-111 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-37 insulin Homo sapiens 225-232 24936246-7 2014 Several studies suggest that ceramides are among the most active lipid second messengers to inhibit the insulin signaling pathway and this review describes the major role played by ceramide accumulation in the development of insulin resistance of peripherals tissues through the targeting of specific proteins of the insulin signaling pathway. Ceramides 29-37 insulin Homo sapiens 225-232 24705014-0 2014 Dynamic GLUT4 sorting through a syntaxin-6 compartment in muscle cells is derailed by insulin resistance-causing ceramide. Ceramides 113-121 insulin Homo sapiens 86-93 24705014-11 2014 Our data are consistent with a model where ceramide could cause insulin resistance by altering intracellular GLUT4 sorting. Ceramides 43-51 insulin Homo sapiens 64-71 25352638-2 2015 Ceramides are well-known mediators of lipid-induced insulin resistance in peripheral organs such as muscle. Ceramides 0-9 insulin Homo sapiens 52-59 25809802-2 2015 The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. Ceramides 79-88 insulin Homo sapiens 168-175 25809802-2 2015 The underlying factor could be accumulation of certain lipid moieties, such as ceramides (CER) and diacylgycerol (DAG) within muscle tissue, which are known to promote insulin resistance (IR), induce inflammation and oxidative injury, ultimately altering muscle function. Ceramides 90-93 insulin Homo sapiens 168-175 26089893-9 2015 Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Ceramides 97-105 insulin Homo sapiens 46-53 25295788-1 2014 Ceramides increase during obesity and promote insulin resistance. Ceramides 0-9 insulin Homo sapiens 46-53 25126394-3 2014 It has been suggested that increased amount of lipids inside the skeletal muscle (intramuscular triglyceride, diacylglycerol and ceramides) will impair insulin action in skeletal muscle, but data are not consistent in the human literature. Ceramides 129-138 insulin Homo sapiens 152-159 24650522-0 2014 Ceramide inhibits insulin-stimulated Akt phosphorylation through activation of Rheb/mTORC1/S6K signaling in skeletal muscle. Ceramides 0-8 insulin Homo sapiens 18-25 24650522-1 2014 Ceramide is a negative regulator of insulin activity. Ceramides 0-8 insulin Homo sapiens 36-43 24892004-3 2014 Fatty acid induced synthesis of ceramide is considered to be one of the major causes for insulin resistance. Ceramides 32-40 insulin Homo sapiens 89-96 24606127-4 2014 We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-alpha (PPARalpha)-mediated ceramide synthesis. Ceramides 199-207 insulin Homo sapiens 56-63 28664064-6 2013 In addition, lipid intermediates (e.g., fatty acyl-coenzyme A, diacylglycerol, and ceramide) impair insulin signaling in skeletal muscle. Ceramides 83-91 insulin Homo sapiens 100-107 24749054-2 2014 Among these lipid species, ceramides and more complex sphingolipids have gained recent attention as being pathophysiologically relevant for the development of insulin resistance and impaired glycemic control. Ceramides 27-36 insulin Homo sapiens 159-166 24749054-3 2014 Upon excess intake of saturated fat, ceramides accumulate in insulin sensitive tissues either as a consequence of de novo synthesis or through mobilization from complex sphingolipids. Ceramides 37-46 insulin Homo sapiens 61-68 24749054-4 2014 Clinical studies have confirmed positive correlation between plasma and tissue levels of several ceramide species and insulin resistance. Ceramides 97-105 insulin Homo sapiens 118-125 24749054-5 2014 At the cellular level, it has been demonstrated that ceramides impair insulin signaling and intracellular handling of glucose and lipids with resulting deleterious effects on cellular metabolism. Ceramides 53-62 insulin Homo sapiens 70-77 24977487-5 2014 Moreover, bioactive lipid intermediates such as diacylglycerol (DAG) and ceramides appear to accumulate in response to NEFA, which may interact with insulin signaling. Ceramides 73-82 insulin Homo sapiens 149-156 24977487-6 2014 However, recent work has also indicated that sphingosine 1-phosphate (S1P), a breakdown product of ceramide, modulate insulin signaling in different cell types. Ceramides 99-107 insulin Homo sapiens 118-125 24376889-10 2013 Observed changes in insulin signaling proteins were related to the content of specific sphingolipids, namely to the reduction of ceramide. Ceramides 129-137 insulin Homo sapiens 20-27 23989724-0 2013 Ceramide accumulation in L6 skeletal muscle cells due to increased activity of ceramide synthase isoforms has opposing effects on insulin action to those caused by palmitate treatment. Ceramides 0-8 insulin Homo sapiens 130-137 23989724-1 2013 AIMS/HYPOTHESIS: An accumulation of ceramides has been implicated in the generation of insulin resistance in skeletal muscle upon an oversupply of fatty acid. Ceramides 36-45 insulin Homo sapiens 87-94 23989724-15 2013 Conversely, certain isoforms promote insulin action, indicating the importance of ceramides in cell function. Ceramides 82-91 insulin Homo sapiens 37-44 24214972-0 2014 Ceramides and glucosylceramides are independent antagonists of insulin signaling. Ceramides 0-9 insulin Homo sapiens 63-70 24214972-3 2014 Of particular note, ceramides antagonize insulin signaling in both myotubes and adipocytes, whereas glucosyceramides are only efficacious in adipocytes: 1) In myotubes exposed to saturated fats, inhibitors of enzymes required for ceramide synthesis enhance insulin signaling, but those targeting glucosylceramide synthase have no effect. Ceramides 20-29 insulin Homo sapiens 41-48 24214972-3 2014 Of particular note, ceramides antagonize insulin signaling in both myotubes and adipocytes, whereas glucosyceramides are only efficacious in adipocytes: 1) In myotubes exposed to saturated fats, inhibitors of enzymes required for ceramide synthesis enhance insulin signaling, but those targeting glucosylceramide synthase have no effect. Ceramides 20-28 insulin Homo sapiens 41-48 24214972-4 2014 2) Exogenous ceramides antagonize insulin signaling in myotubes, whereas ganglioside precursors do not. Ceramides 13-22 insulin Homo sapiens 34-41 23832510-1 2014 UNLABELLED: Obesity is associated with increased activity of two lipid signaling systems (endocannabinoids [ECs] and ceramides), with both being implicated in insulin resistance. Ceramides 117-126 insulin Homo sapiens 159-166 23640896-7 2013 This unique signaling capacity exerted by Rac-1 superactivation bypassed the defects imposed by JNK- and ceramide-induced insulin resistance and allowed full and partial restoration of the GLUT4 translocation response, respectively. Ceramides 105-113 insulin Homo sapiens 122-129 23988586-3 2013 Two separate views suggest that IMTG dynamics are determinant for skeletal muscle fat oxidation, and that disruption of IMTG dynamics facilitates the accumulation of lipotoxic intermediates such as diacylglycerols and ceramides that interfere with insulin signaling. Ceramides 218-227 insulin Homo sapiens 248-255 24269881-1 2013 UNLABELLED: High lipid and ceramide concentrations are hallmarks of obese and/or insulin resistant skeletal muscle, yet little is known about its role on cell cycle and senescence. Ceramides 27-35 insulin Homo sapiens 81-88 24269881-7 2013 Metformin limited (p<0.05) ceramide"s effects on insulin signaling, senescence, and cell cycle regulation. Ceramides 30-38 insulin Homo sapiens 52-59 23640896-0 2013 Rac-1 superactivation triggers insulin-independent glucose transporter 4 (GLUT4) translocation that bypasses signaling defects exerted by c-Jun N-terminal kinase (JNK)- and ceramide-induced insulin resistance. Ceramides 173-181 insulin Homo sapiens 31-38 23640896-0 2013 Rac-1 superactivation triggers insulin-independent glucose transporter 4 (GLUT4) translocation that bypasses signaling defects exerted by c-Jun N-terminal kinase (JNK)- and ceramide-induced insulin resistance. Ceramides 173-181 insulin Homo sapiens 190-197 23640727-10 2013 Increases in ceramides were noted, which left unchecked may promote systemic insulin resistance. Ceramides 13-22 insulin Homo sapiens 77-84 23896361-6 2013 Dyslipidemic small HDL particles were further distinguished not only as the primary carrier of ceramides, which promote inflammation and insulin resistance, but also by a subnormal plasmalogen/apoAI ratio, consistent with elevated oxidative stress typical of type 2 diabetes. Ceramides 95-104 insulin Homo sapiens 137-144 23835113-5 2013 Studies using cultured cells, animal models, and human subjects demonstrate that ceramide is a key player in the induction of beta-cell apoptosis, insulin resistance, and reduction of insulin gene expression. Ceramides 81-89 insulin Homo sapiens 147-154 23835113-7 2013 Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramides 0-8 insulin Homo sapiens 36-43 23835113-7 2013 Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramides 0-8 insulin Homo sapiens 76-83 23835113-7 2013 Ceramide also modulates many of the insulin signaling intermediates such as insulin receptor substrate, Akt, Glut-4, and it causes insulin resistance. Ceramides 0-8 insulin Homo sapiens 76-83 23835113-8 2013 Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. Ceramides 0-8 insulin Homo sapiens 34-41 23835113-8 2013 Ceramide reduces the synthesis of insulin hormone by attenuation of insulin gene expression. Ceramides 0-8 insulin Homo sapiens 68-75 23386653-2 2013 In this study we measured whether GC-induced insulin resistance in humans is related to changes in muscle ceramide, GM3, and muscle mitochondrial function. Ceramides 106-114 insulin Homo sapiens 45-52 23529132-5 2013 Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBalpha protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. Ceramides 228-236 insulin Homo sapiens 0-7 23393182-8 2013 Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Ceramides 7-15 insulin Homo sapiens 55-62 23393182-8 2013 Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Ceramides 7-15 insulin Homo sapiens 76-83 23305978-9 2013 These associations suggest that the insulin-sensitizing effect of adiponectin on human male skeletal muscles may be mediated via AdipoR1 to activation of AMPK, leading to lowering of ceramide content. Ceramides 183-191 insulin Homo sapiens 36-43 26052434-4 2012 Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. Ceramides 145-154 insulin Homo sapiens 185-192 23139352-2 2013 Here, we explored the role of circulating ceramide on the pathogenesis of insulin resistance. Ceramides 42-50 insulin Homo sapiens 74-81 23139352-3 2013 Ceramide transported in LDL is elevated in the plasma of obese patients with type 2 diabetes and correlated with insulin resistance but not with the degree of obesity. Ceramides 0-8 insulin Homo sapiens 113-120 23139352-4 2013 Treating cultured myotubes with LDL containing ceramide promoted ceramide accrual in cells and was accompanied by reduced insulin-stimulated glucose uptake, Akt phosphorylation, and GLUT4 translocation compared with LDL deficient in ceramide. Ceramides 47-55 insulin Homo sapiens 122-129 23250746-3 2013 Ceramides are sphingolipids that modulate a variety of cellular responses including cell death, autophagy, insulin signaling, and inflammation. Ceramides 0-9 insulin Homo sapiens 107-114 23612696-1 2013 Accumulation of ceramides within tissues induces insulin resistance. Ceramides 16-25 insulin Homo sapiens 49-56 23612696-3 2013 We hypothesized that specific plasma ceramide subspecies are elevated in obese children and adolescents with type 2 diabetes (T2D), and that they inversely correlate with adiponectin and measures of insulin sensitivity. Ceramides 37-45 insulin Homo sapiens 199-206 23054552-2 2012 Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. Ceramides 36-45 insulin Homo sapiens 124-131 22677645-1 2012 Ceramides (Cer) are implicated in obesity-associated skeletal muscle and perhaps adipocyte insulin resistance. Ceramides 0-9 insulin Homo sapiens 91-98 22677645-1 2012 Ceramides (Cer) are implicated in obesity-associated skeletal muscle and perhaps adipocyte insulin resistance. Ceramides 0-3 insulin Homo sapiens 91-98 22801434-2 2012 Insulin-resistance dysregulates lipid metabolism, which promotes ceramide accumulation with attendant inflammation and endoplasmic reticulum (ER) stress. Ceramides 65-73 insulin Homo sapiens 0-7 22801434-3 2012 Mechanistically, we propose that toxic ceramides generated in extra-CNS tissues, e.g. liver, get released into peripheral blood, and subsequently transit across the blood-brain barrier into the brain where they induce brain insulin-resistance, inflammation, and cell death (extrinsic pathway). Ceramides 39-48 insulin Homo sapiens 224-231 22801434-4 2012 These abnormalities establish or help propagate a cascade of neurodegeneration associated with increased ER stress and ceramide generation, which exacerbate brain insulin-resistance, cell death, myelin degeneration, and neuro-inflammation. Ceramides 119-127 insulin Homo sapiens 163-170 22176347-2 2012 We hypothesized that in NAFLD, insulin resistance dysregulates lipid metabolism, increasing production of cytotoxic lipids including ceramides, which exacerbate hepatic insulin resistance and injury. Ceramides 133-142 insulin Homo sapiens 31-38 22425588-1 2012 Data from studies in animal models indicate that certain lipid metabolites, particularly diacylglycerol, ceramide, and acylcarnitine, disrupt insulin action. Ceramides 105-113 insulin Homo sapiens 142-149 22586279-4 2012 Systemic insulin resistance in heart failure was accompanied by decreased myocardial triglyceride and overall fatty acid content but increased toxic lipid intermediates, diacylglycerol, and ceramide. Ceramides 190-198 insulin Homo sapiens 9-16 22560211-0 2012 A ceramide-centric view of insulin resistance. Ceramides 2-10 insulin Homo sapiens 27-34 22560211-2 2012 In this review, we discuss from a historical perspective the most important discoveries produced over the last decade supporting a role for ceramide and its metabolites in the pathogenesis of insulin resistance and other obesity-associated metabolic diseases. Ceramides 140-148 insulin Homo sapiens 192-199 22560211-3 2012 Moreover, we describe how a ceramide-centric view of insulin resistance might be reconciled in the context of other prominent models of nutrient-induced insulin resistance. Ceramides 28-36 insulin Homo sapiens 53-60 22176347-7 2012 Ceramide treatment impaired Huh7 cell viability, mitochondrial function, and insulin signaling. Ceramides 0-8 insulin Homo sapiens 77-84 21437908-1 2012 Ceramide is involved in development of insulin resistance. Ceramides 0-8 insulin Homo sapiens 39-46 22176347-8 2012 CONCLUSIONS: Increased hepatic ceramide generation and release may mediate both hepatic and peripheral insulin resistance in NAFLD. Ceramides 33-41 insulin Homo sapiens 105-112 22385956-4 2012 Ultimately, these cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance. Ceramides 130-139 insulin Homo sapiens 214-221 22320914-5 2012 Chronic alcohol consumption produces steatohepatitis, which also promotes hepatic insulin resistance, oxidative stress and injury, with the attendant increased generation of "toxic lipids" such as ceramides that increase insulin resistance. Ceramides 197-206 insulin Homo sapiens 221-228 22320914-8 2012 We postulate that the neurotoxic and neurodegenerative effects of liver-derived ceramides activate pro-inflammatory cytokines and increase lipid adducts and insulin resistance in the brain to impair cognitive and motor function. Ceramides 80-89 insulin Homo sapiens 157-164 22577490-7 2012 Given the role of ceramides as mediators of ER stress and insulin resistance, treatment with ceramide enzyme inhibitors may help reverse or halt progression of chronic ALD. Ceramides 18-27 insulin Homo sapiens 58-65 22297646-4 2012 The rationale is that insulin resistance dysregulates lipid metabolism and promotes ceramide accumulation, and thereby increases inflammation and stress. Ceramides 84-92 insulin Homo sapiens 22-29 22337830-1 2012 Ceramides are lipid signaling molecules that cause cytotoxicity and cell death mediated by insulin resistance, inflammation, and endoplasmic reticulum (ER) stress. Ceramides 0-9 insulin Homo sapiens 91-98 22337830-2 2012 However, insulin resistance dysregulates lipid metabolism, which promotes ceramide accumulation with attendant inflammation and ER stress. Ceramides 74-82 insulin Homo sapiens 9-16 22337830-5 2012 Mechanistically, we propose that toxic ceramides generated in extra-CNS tissues (e.g., liver) get released into peripheral blood, and subsequently transit across the blood-brain barrier into the brain where they induce brain insulin resistance, inflammation, and cell death (extrinsic pathway). Ceramides 39-48 insulin Homo sapiens 225-232 22337830-7 2012 The end result is increased ER stress and ceramide generation, which exacerbate brain insulin resistance, cell death, myelin degeneration, and neuroinflammation. Ceramides 42-50 insulin Homo sapiens 86-93 21546935-10 2011 At 6 months, the improvement in insulin sensitivity correlated with the change in total ceramide levels (r = -0.68, P = 0.02), and with plasma tumor necrosis factor-alpha (TNF-alpha) (r = -0.62, P = 0.04). Ceramides 88-96 insulin Homo sapiens 32-39 22120643-3 2012 Research during the last two decades has provided evidence for a role of lipid intermediates like diacylglycerol and ceramide in the induction of lipid-induced insulin resistance. Ceramides 117-125 insulin Homo sapiens 160-167 21546935-11 2011 We conclude that there is a potential role for ceramide lipids as mediators of the proinflammatory state and improved insulin sensitivity after gastric bypass surgery. Ceramides 47-62 insulin Homo sapiens 118-125 21336841-4 2011 However, they provide a source for the generation of harmful lipid metabolites such as diacylglycerol and ceramide, which are implicated in insulin resistance by perturbing insulin signaling pathways. Ceramides 106-114 insulin Homo sapiens 140-147 21873552-0 2011 Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes? Ceramides 52-61 insulin Homo sapiens 65-72 21873552-9 2011 Ceramide content was higher in insulin-resistant obese muscle. Ceramides 0-8 insulin Homo sapiens 31-38 21873552-12 2011 Our data also provide additional evidence in humans linking ceramides to insulin resistance. Ceramides 60-69 insulin Homo sapiens 73-80 21635197-6 2011 Ceramide contributes to endoplasmatic reticulum (ER) stress, decreased mitochondrial membrane potential in insulin-secreting cells and mitochondrial release of cytochrome c into the cytosol, which are all triggers of apoptotic cell death. Ceramides 0-8 insulin Homo sapiens 107-114 21635197-8 2011 Ceramide reduces the activity of voltage gated potassium (Kv)-channels in insulin-secreting cells. Ceramides 0-8 insulin Homo sapiens 74-81 21336841-4 2011 However, they provide a source for the generation of harmful lipid metabolites such as diacylglycerol and ceramide, which are implicated in insulin resistance by perturbing insulin signaling pathways. Ceramides 106-114 insulin Homo sapiens 173-180 21735505-2 2011 Excess accumulation of intracellular LCACoA, diacylglycerols (DAGs) and ceramides may create insulin resistance with respect to glucose metabolism. Ceramides 72-81 insulin Homo sapiens 93-100 21677348-4 2011 Accumulation of intracellular lipids such as diacylglycerols (DAG) and ceramides (CER) was found to interfere directly with the insulin signaling cascade, inducing hepatic IR. Ceramides 71-80 insulin Homo sapiens 128-135 21794038-2 2011 Ceramides and other toxic sphingolipids promote inflammation, lipotoxicity and insulin resistance; however, the role of ceramides in the pathogenesis of NASH has not been determined. Ceramides 0-9 insulin Homo sapiens 79-86 21431854-1 2011 Based on the "lipotoxic" hypothesis, the free fatty acid flux from the excessive amount of adipose tissue toward the peripheral tissues would induce the development of insulin resistance especially when the triglyceride storage or the concentration of intermediate fat metabolites (diacylglycerides, ceramides) within the cytoplasm of these cells become excessive. Ceramides 300-309 insulin Homo sapiens 168-175 21327867-1 2011 AIMS/HYPOTHESIS: Intramyocellular lipids, including diacylglycerol (DAG) and ceramides, have been linked to insulin resistance. Ceramides 77-86 insulin Homo sapiens 108-115 21570480-5 2011 PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IkappaBalpha degradation or mTOR activation. Ceramides 85-93 insulin Homo sapiens 11-18 21570480-10 2011 CONCLUSIONS: PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. Ceramides 128-136 insulin Homo sapiens 24-31 21677348-4 2011 Accumulation of intracellular lipids such as diacylglycerols (DAG) and ceramides (CER) was found to interfere directly with the insulin signaling cascade, inducing hepatic IR. Ceramides 82-85 insulin Homo sapiens 128-135 20876726-0 2010 Targeting ceramide synthesis to reverse insulin resistance. Ceramides 10-18 insulin Homo sapiens 40-47 21176778-5 2011 Understanding how DAG- and ceramide-activated PKCs impair insulin signalling would help to develop treatments to fight insulin resistance. Ceramides 27-35 insulin Homo sapiens 58-65 20561942-7 2011 It is not yet clear, however whether ceramides or glycosphingolipids are involved as both have been implicated to be inhibitors of the insulin signaling cascade. Ceramides 37-46 insulin Homo sapiens 135-142 20876761-4 2010 Blocking de novo synthesis of ceramide abolished the effects of palmitate on mtROS production, viability, and insulin signaling. Ceramides 30-38 insulin Homo sapiens 110-117 19959757-0 2010 Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Ceramides 85-93 insulin Homo sapiens 104-111 20361178-6 2010 Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Ceramides 73-81 insulin Homo sapiens 160-167 20393162-1 2010 The molecular mechanisms of obesity-associated insulin resistance are becoming increasingly clear, and the effects of various lipid molecules, such as diacylglycerol and ceramide, on the insulin signal are being actively explored. Ceramides 170-178 insulin Homo sapiens 187-194 20216312-3 2010 RECENT FINDINGS: Who: ceramides and glucosylceramides are likely to be independent antagonists of insulin action. Ceramides 22-31 insulin Homo sapiens 98-105 20216312-4 2010 Where: recent data suggest that ceramides may inhibit insulin action in skeletal muscle, whereas glucosylceramides may be more efficacious in adipose tissue. Ceramides 32-41 insulin Homo sapiens 54-61 20216312-6 2010 What: ceramides and glucosylceramides inhibit different insulin signaling events, but it is unclear whether these actions account for the broad spectrum of therapeutic benefits resulting from sphingolipid depletion. Ceramides 6-15 insulin Homo sapiens 56-63 19958841-2 2010 Prominent among these so-called lipotoxic mediators are signaling molecules such as long chain acyl-CoAs, ceramides and diacyglycerols; each of which is thought to engage serine kinases that disrupt the insulin signaling cascade, thereby causing insulin resistance. Ceramides 106-115 insulin Homo sapiens 203-210 19958841-2 2010 Prominent among these so-called lipotoxic mediators are signaling molecules such as long chain acyl-CoAs, ceramides and diacyglycerols; each of which is thought to engage serine kinases that disrupt the insulin signaling cascade, thereby causing insulin resistance. Ceramides 106-115 insulin Homo sapiens 246-253 19959757-1 2010 OBJECTIVE: Ceramide is now recognized as a negative regulator of insulin signaling by impairing protein kinase B (PKB)/Akt activation. Ceramides 11-19 insulin Homo sapiens 65-72 19782765-5 2010 Accumulation of fatty acids and lipid metabolites (such as long chain acyl CoA, diacylglycerol, triacylglycerol, and/or ceramide) can lead to alterations in this insulin signaling pathway. Ceramides 120-128 insulin Homo sapiens 162-169 20425071-4 2010 Ceramide has been implicated in the pathogenesis of insulin resistance and has many proinflammatory properties. Ceramides 0-8 insulin Homo sapiens 52-59 19669729-0 2009 Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease. Ceramides 20-29 insulin Homo sapiens 48-55 19833891-0 2010 Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Ceramides 135-143 insulin Homo sapiens 0-7 19777393-3 2009 T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Ceramides 64-72 insulin Homo sapiens 134-141 19556298-10 2009 This was associated with increased ceramide production, and use of the ceramide inhibitors myriocin and fumonisin B1 partially recovered the insulin sensitivity. Ceramides 71-79 insulin Homo sapiens 141-148 19777393-3 2009 T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Ceramides 183-192 insulin Homo sapiens 134-141 19777393-3 2009 T2DM/NASH has been demonstrated to be associated with increased ceramide generation, suggesting a mechanistic link between peripheral insulin resistance and neurodegeneration because ceramides mediate insulin resistance and can cross the blood-brain barrier (BBB). Ceramides 183-192 insulin Homo sapiens 201-208 19777393-4 2009 Peripheral insulin resistance diseases may potentially cause brain insulin resistance via a liver-brain axis of neurodegeneration as a result of the trafficking of ceramides across the BBB. Ceramides 164-173 insulin Homo sapiens 11-18 19777393-4 2009 Peripheral insulin resistance diseases may potentially cause brain insulin resistance via a liver-brain axis of neurodegeneration as a result of the trafficking of ceramides across the BBB. Ceramides 164-173 insulin Homo sapiens 67-74 18548166-6 2008 In vitro data indicate that ceramide inhibits insulin signaling, mainly through inactivation of protein kinase B. Ceramides 28-36 insulin Homo sapiens 46-53 19712582-5 2009 Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. Ceramides 193-202 insulin Homo sapiens 97-104 19712582-5 2009 Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. Ceramides 193-202 insulin Homo sapiens 250-257 19712582-6 2009 In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production. Ceramides 212-220 insulin Homo sapiens 47-54 19303901-3 2009 Ceramide, the most simple sphingolipid, directly inhibits phosphorylation of the insulin signaling mediator Akt/Protein Kinase B. Ceramides 0-8 insulin Homo sapiens 81-88 19008343-0 2009 Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Ceramides 7-16 insulin Homo sapiens 104-111 19008343-2 2009 Ceramides are a putative mediator of insulin resistance and lipotoxicity, and accumulation of ceramides within tissues in obese and diabetic subjects has been well described. Ceramides 0-9 insulin Homo sapiens 37-44 19008343-8 2009 Insulin sensitivity was inversely correlated with C18:0, C20:0, C24:1, C24:0, and total ceramide (all P < 0.01). Ceramides 88-96 insulin Homo sapiens 0-7 19008343-10 2009 CONCLUSIONS: Plasma ceramide levels are elevated in type 2 diabetic subjects and may contribute to insulin resistance through activation of inflammatory mediators, such as TNF-alpha. Ceramides 20-28 insulin Homo sapiens 99-106 19387107-4 2009 Since ceramides are neurotoxic and cause insulin resistance, we directly investigated the role of ceramides as mediators of neurodegeneration using an in vitro culture model. Ceramides 6-15 insulin Homo sapiens 41-48 18397976-2 2008 Intramyocellular sphingolipids (i.e. ceramide) have been suggested to induce insulin resistance by interfering with the insulin signaling cascade in obesity. Ceramides 37-45 insulin Homo sapiens 77-84 18397976-2 2008 Intramyocellular sphingolipids (i.e. ceramide) have been suggested to induce insulin resistance by interfering with the insulin signaling cascade in obesity. Ceramides 37-45 insulin Homo sapiens 120-127 18460913-4 2008 RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Ceramides 104-113 insulin Homo sapiens 125-132 18451260-6 2008 Herein we will review the role of ceramide and other sphingolipid metabolites in insulin resistance, beta-cell failure, cardiomyopathy, and vascular dysfunction, focusing on these in vivo studies that identify enzymes controlling sphingolipid metabolism as therapeutic targets for combating metabolic disease. Ceramides 34-42 insulin Homo sapiens 81-88 19742171-2 2009 Alcohol-induced steatohepatitis promotes synthesis and accumulation of ceramides and other toxic lipids that cause insulin resistance. Ceramides 71-80 insulin Homo sapiens 115-122 19742171-3 2009 Ceramides can readily cross the blood-brain barrier, and ceramide exposure causes neurodegeneration with insulin resistance and oxidative stress, similar to the effects of alcohol. Ceramides 57-65 insulin Homo sapiens 105-112 18458870-0 2008 Ceramide: a contributor to insulin resistance or an innocent bystander? Ceramides 0-8 insulin Homo sapiens 27-34 18458871-1 2008 AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. Ceramides 37-46 insulin Homo sapiens 86-93 18458871-1 2008 AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. Ceramides 37-46 insulin Homo sapiens 131-138 18458871-9 2008 Interestingly, a positive correlation (r=0.42, p<0.05) was present between muscle ceramide content at baseline and insulin sensitivity. Ceramides 85-93 insulin Homo sapiens 118-125 18364460-4 2008 In addition, insulin-resistant skeletal muscle cells exhibit enhanced production of reactive oxygen species and ceramide as well as a downregulation of myogenic transcription factors such as myogenin and MyoD. Ceramides 112-120 insulin Homo sapiens 13-20 18207474-5 2008 Hence it is believed that intermediates in fatty acid metabolism, such as fatty acyl-CoA, ceramides or diacylglycerol (DAG) link fat deposition in the muscle to compromised insulin signaling. Ceramides 90-99 insulin Homo sapiens 173-180 18548166-7 2008 In vivo data suggest that ceramide accumulation within muscle cells might be associated with the development of insulin resistance. Ceramides 26-34 insulin Homo sapiens 112-119