PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 3280335-1 1988 Insulin stimulation of glycogen synthesis was nearly abolished in hepatoma cells shortly treated with 4 beta-phorbol 12 beta-myristate, 13 alpha-acetate (protein kinase C activation) but remained unmodified in cells chronically treated with the phorbol ester (protein kinase C depletion). Phorbol Esters 245-258 insulin Homo sapiens 0-7 2820811-6 1987 Catecholamine and phorbol ester induced insulin resistance of isolated rat fat cells as well as human fat cells was associated with a decreased activity of the insulin receptor tyrosine kinase which was apparently due to a modulation of the ATP binding site of the insulin receptor tyrosine kinase; 3. Phorbol Esters 18-31 insulin Homo sapiens 40-47 3304983-0 1987 Phorbol ester inhibition of insulin-stimulated deoxyribonucleic acid synthesis in BC3H-1 myocytes. Phorbol Esters 0-13 insulin Homo sapiens 28-35 3304983-4 1987 Phorbol ester inhibition of insulin-stimulated DNA synthesis was specific for the active tumor-promoting phorbols and the synthetic diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol. Phorbol Esters 0-13 insulin Homo sapiens 28-35 2820811-6 1987 Catecholamine and phorbol ester induced insulin resistance of isolated rat fat cells as well as human fat cells was associated with a decreased activity of the insulin receptor tyrosine kinase which was apparently due to a modulation of the ATP binding site of the insulin receptor tyrosine kinase; 3. Phorbol Esters 18-31 insulin Homo sapiens 160-167 2820811-6 1987 Catecholamine and phorbol ester induced insulin resistance of isolated rat fat cells as well as human fat cells was associated with a decreased activity of the insulin receptor tyrosine kinase which was apparently due to a modulation of the ATP binding site of the insulin receptor tyrosine kinase; 3. Phorbol Esters 18-31 insulin Homo sapiens 160-167 3526339-4 1986 These results indicate that activators of protein kinase C, such as phorbol esters, desensitize cells to insulin by direct protein kinase C action on the insulin receptor. Phorbol Esters 68-82 insulin Homo sapiens 105-112 3300647-0 1987 Insulin-dependent alterations of phorbol ester binding to adipocyte subcellular constituents. Phorbol Esters 33-46 insulin Homo sapiens 0-7 3300647-4 1987 Treatment of cells with physiological concentration of insulin (0.67 nM) caused a 42% increase (from 0.92 +/- 0.08 to 1.30 +/- 0.12 pmol 3H-PBu2/mg protein, p less than 0.0001) and a 27% decrease (from 0.41 +/- 0.07 to 0.30 +/- 0.05 pmol 3H-PBu2/mg protein, p less than 0.020) in phorbol ester bound to cytosol and plasma membranes, respectively. Phorbol Esters 280-293 insulin Homo sapiens 55-62 3539101-0 1986 Potentiation of specific association of insulin with HepG2 cells by phorbol esters. Phorbol Esters 68-82 insulin Homo sapiens 40-47 3539101-4 1986 The phorbol-ester-induced enhancement of internalized insulin in HepG2 cells was additive with the potentiation of endocytosed insulin induced by both the lysosomotropic reagent chloroquine and the ionophore monensin; this indicates that TPA affects the intracellular processing of the insulin receptor at a point other than those disrupted by either of these two reagents. Phorbol Esters 4-17 insulin Homo sapiens 54-61 3539101-4 1986 The phorbol-ester-induced enhancement of internalized insulin in HepG2 cells was additive with the potentiation of endocytosed insulin induced by both the lysosomotropic reagent chloroquine and the ionophore monensin; this indicates that TPA affects the intracellular processing of the insulin receptor at a point other than those disrupted by either of these two reagents. Phorbol Esters 4-17 insulin Homo sapiens 127-134 3539101-6 1986 By these criteria, the effects of phorbol esters on the insulin receptor in HepG2 cells appear to be mediated through protein kinase C. These results support the concept that the activation of protein kinase C by treatment with phorbol esters causes a perturbation of the insulin-receptor-mediated endocytotic pathway in HepG2 cells, reflected in a long-term decreased rate of dissociation of internalized insulin by the phorbol-ester-treated cells. Phorbol Esters 34-48 insulin Homo sapiens 56-63 3539101-6 1986 By these criteria, the effects of phorbol esters on the insulin receptor in HepG2 cells appear to be mediated through protein kinase C. These results support the concept that the activation of protein kinase C by treatment with phorbol esters causes a perturbation of the insulin-receptor-mediated endocytotic pathway in HepG2 cells, reflected in a long-term decreased rate of dissociation of internalized insulin by the phorbol-ester-treated cells. Phorbol Esters 228-242 insulin Homo sapiens 56-63 3539101-6 1986 By these criteria, the effects of phorbol esters on the insulin receptor in HepG2 cells appear to be mediated through protein kinase C. These results support the concept that the activation of protein kinase C by treatment with phorbol esters causes a perturbation of the insulin-receptor-mediated endocytotic pathway in HepG2 cells, reflected in a long-term decreased rate of dissociation of internalized insulin by the phorbol-ester-treated cells. Phorbol Esters 421-434 insulin Homo sapiens 56-63 3927905-3 1985 It is reversible in 60 min at 37 degrees C. A suboptimal concentration of the ionophore potentiates the inhibitory action of phorbol esters on insulin binding. Phorbol Esters 125-139 insulin Homo sapiens 143-150 2864925-3 1985 The tumor promoting phorbol esters have been reported to stimulate phosphorylation of the insulin receptor and thereby decrease the ability of insulin to induce tyrosine aminotransferase. Phorbol Esters 20-34 insulin Homo sapiens 90-97 2986534-13 1985 The insulin receptor kinase is also inhibited in intact cells by phorbol esters that mediate serine/threonine phosphorylation of the insulin receptor, presumably via the Ca++-phospholipid-dependent protein kinase. Phorbol Esters 65-79 insulin Homo sapiens 4-11 3158511-0 1985 Phorbol ester provokes insulin-like effects on glucose transport, amino acid uptake, and pyruvate dehydrogenase activity in BC3H-1 cultured myocytes. Phorbol Esters 0-13 insulin Homo sapiens 23-30 3158511-6 1985 The insulin-like effects in the myocytes appeared to be specific for TPA, the biologically active phorbol diester which activates protein kinase C, as other tested phorbol derivatives were without effect. Phorbol Esters 98-113 insulin Homo sapiens 4-11 6376081-2 1984 In cell culture, insulin interacts synergistically with other hormones and growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), tumor-promoting phorbol esters, and thrombin, to stimulate progression through the cell cycle of cells that have been arrested in G1 by deprivation for serum. Phorbol Esters 216-230 insulin Homo sapiens 17-24 25002582-8 2014 Using (32)P labeling and mass spectrometry, we showed that tomosyn-2 is phosphorylated in response to high glucose, phorbol esters, and analogs of cAMP, all key insulin secretagogues. Phorbol Esters 116-130 insulin Homo sapiens 161-168 6312447-0 1983 Phorbol esters stimulate the phosphorylation of receptors for insulin and somatomedin C. Phorbol Esters 0-14 insulin Homo sapiens 62-69 6312447-1 1983 The effect of phorbol esters on the extent of phosphorylation of receptors for insulin and somatomedin C (insulin-like growth factor I) was studied in intact IM-9 cells that were labeled by incubation with H332PO4. Phorbol Esters 14-28 insulin Homo sapiens 79-86 6891320-1 1982 Phorbol esters inhibit the binding of insulin to its receptors on U-937 monocyte-like and HL-60 promyelocytic leukemia human cell lines. Phorbol Esters 0-14 insulin Homo sapiens 38-45 6751097-5 1982 Insulin binding is decreased by TPA whether the phorbol ester is added before, after, or simultaneously with 125I-insulin to the cell suspension. Phorbol Esters 48-61 insulin Homo sapiens 0-7 12614163-6 2003 Luc activity in Hep G2 cells transfected with pIRCE-Luc was stimulated by insulin, an insulin mimetic bisperoxo (1,10-phenanthroline) oxovanadate (bpv) and the phorbol ester (PDBu). Phorbol Esters 160-173 insulin Homo sapiens 74-81 21205932-5 2011 We demonstrate that PKC activation with either a phorbol ester or exogenous application of diacylglycerides impairs insulin-induced Akt activation, whereas PKC inhibition augments insulin-induced Akt activation. Phorbol Esters 49-62 insulin Homo sapiens 116-123 21136963-5 2009 The results of the arrayed antibodies were verified by the multiplexed bead array assay and conventional Western blot analysis, and confirmed the well-known inhibitory effects of phorbol esters on insulin signaling pathway activation. Phorbol Esters 179-193 insulin Homo sapiens 197-204 18215133-3 2008 In a similar manner to insulin, phorbol esters also activate mTORC1 signalling, in this case via PKC (protein kinase C) and ERK (extracellular-signal-regulated kinase). Phorbol Esters 32-46 insulin Homo sapiens 23-30 12376314-0 2002 Potentiation of insulin secretion by phorbol esters is mediated by PKC-alpha and nPKC isoforms. Phorbol Esters 37-51 insulin Homo sapiens 16-23 12376314-1 2002 Culturing clonal beta-cells (HIT-T15) overnight in the presence of phorbol ester [phorbol myristate acetate (PMA)] enhanced insulin secretion while causing downregulation of some protein kinase C (PKC) isoforms and most PKC activity. Phorbol Esters 67-80 insulin Homo sapiens 124-131 11915930-4 2001 Incubating human muscle fiber strips with PKC inhibitors restored insulin action in muscle of obese patients, while activating PKC with a phorbol ester caused insulin resistance in muscle from lean control patients. Phorbol Esters 138-151 insulin Homo sapiens 159-166 10830281-4 2000 Down-regulation of PKC by phorbol esters was confirmed by Western blotting and resulted in the complete loss of cPKC activity, partial loss of nPKC activity and preservation of aPKC activity and glucose-stimulated insulin secretion. Phorbol Esters 26-40 insulin Homo sapiens 214-221 11672436-0 2001 Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression. Phorbol Esters 24-38 insulin Homo sapiens 42-49 11672436-0 2001 Antagonistic effects of phorbol esters on insulin regulation of insulin-like growth factor-binding protein-1 (IGFBP-1) but not glucose-6-phosphatase gene expression. Phorbol Esters 24-38 insulin Homo sapiens 64-71 11672436-4 2001 However, we find that treatment of cells with phorbol esters mimics the effect of insulin on G6Pase, but not IGFBP-1, gene expression. Phorbol Esters 46-60 insulin Homo sapiens 82-89 11672436-5 2001 Indeed, phorbol ester treatment actually blocks the ability of insulin to repress IGFBP-1 gene expression. Phorbol Esters 8-21 insulin Homo sapiens 63-70 9387094-8 1997 It is activated by glucose, insulin, low oxygen "hypoxic" conditions, and phorbol esters, all of which enhance the rate of transcription. Phorbol Esters 74-88 insulin Homo sapiens 28-35 10373474-8 1999 Moreover, phorbol esters were a much more potent inducer of collagenase-CAT gene transcription than insulin, a difference that may be explained by selective effects of insulin and phorbol esters on AP-1 expression. Phorbol Esters 10-24 insulin Homo sapiens 168-175 9877233-3 1998 Similarly, insulin release induced by the phorbol ester TPA (protein kinase C activator) was markedly potentiated. Phorbol Esters 42-55 insulin Homo sapiens 11-18 9607141-0 1998 Potentiation of insulin-induced phosphatidylinositol-3 kinase activity by phorbol ester is mediated by protein kinase C epsilon. Phorbol Esters 74-87 insulin Homo sapiens 16-23 9402139-17 1997 Phorbol ester stimulation of IGFBP-1 expression can supersede the effects of insulin in vitro;however, the mechanism and in vivo correlates of this effect have not been determined. Phorbol Esters 0-13 insulin Homo sapiens 77-84 8897815-3 1996 Stimulation of insulin release evoked by glucose, phospholipase C activation with carbachol, and protein kinase C activation with phorbol ester were obtained by SIN-1, whereas the response to adenylyl cyclase activation or K(+)-induced depolarization was not affected. Phorbol Esters 130-143 insulin Homo sapiens 15-22 8650266-4 1996 By contrast, although phorbol esters mimic the action of insulin on the regulation of PEPCK gene transcription, wortmannin does not block the effect of these agents. Phorbol Esters 22-36 insulin Homo sapiens 57-64 8663368-5 1996 Translocation of PKC to the membrane by incubation of HIT cells for 10 min in the presence of 20 nM phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a 5-fold increase in glucose-induced insulin release. Phorbol Esters 100-113 insulin Homo sapiens 206-213 8842533-0 1996 Insulin translocates PKC-epsilon and phorbol esters induce and persistently translocate PKC-beta 2 in BC3H-1 myocytes. Phorbol Esters 37-51 insulin Homo sapiens 0-7 7797543-7 1995 Phorbol esters mimic the action of insulin on the regulation of PEPCK gene expression, but wortmannin does not block the effect of these agents. Phorbol Esters 0-14 insulin Homo sapiens 35-42 8561786-0 1996 Choline phosphate and phorbol ester potentiate the mitogenic effect of insulin by competitive mechanisms in NIH 3T3 fibroblasts. Phorbol Esters 22-35 insulin Homo sapiens 71-78 7857262-2 1995 Synthetic diacylglycerol or phorbol ester can mimic the effect of insulin on G3PDH activity, suggesting that protein kinase C may be involved in regulation of G3PDH levels. Phorbol Esters 28-41 insulin Homo sapiens 66-73 7929343-3 1994 In these studies, we demonstrate that phorbol ester treatment of intact COS-1 cells transiently expressing the human insulin receptor stimulates phosphorylation of serine 1327 within the carboxyl-terminal tail of the insulin receptor beta subunit. Phorbol Esters 38-51 insulin Homo sapiens 117-124 7770008-5 1995 After 24 h the protein kinase C (PKC) activator phorbol ester (PMA) increases the insulin binding to a similar degree as does the insulin imprinting itself. Phorbol Esters 48-61 insulin Homo sapiens 82-89 7523864-0 1994 Identification of cis-elements mediating the stimulation of rat insulin-like growth factor-binding protein-1 promoter activity by dexamethasone, cyclic adenosine 3",5"-monophosphate, and phorbol esters, and inhibition by insulin. Phorbol Esters 187-201 insulin Homo sapiens 64-71 8063733-3 1994 Using a gel shift assay we found that formation of the ternary complex increased transiently within 2 min of insulin or phorbol ester treatment of several insulin-sensitive cell lines. Phorbol Esters 120-133 insulin Homo sapiens 155-162 1650476-8 1991 Thus, although it has been previously shown that insulin and phorbol esters repress PEPCK gene transcription through distinct pathways, the final target of insulin and phorbol ester action is the same DNA element. Phorbol Esters 61-75 insulin Homo sapiens 156-163 1322137-15 1992 The phorbol ester phorbol 12-myristate 13-acetate (PMA) also increased insulin promoter-driven CAT expression in the presence of 1 mM-, but not 11 mM-glucose. Phorbol Esters 4-17 insulin Homo sapiens 71-78 1572414-5 1992 When insulin was added to phorbol ester-pretreated cells the insulin-induced increase in beta-actin transcription was reduced by 40-60%. Phorbol Esters 26-39 insulin Homo sapiens 5-12 1572414-5 1992 When insulin was added to phorbol ester-pretreated cells the insulin-induced increase in beta-actin transcription was reduced by 40-60%. Phorbol Esters 26-39 insulin Homo sapiens 61-68 1946468-4 1991 Also, insulin and IGF-II potentiated the phorbol ester-induced differentiation, although less efficiently than IGF-I. Phorbol Esters 41-54 insulin Homo sapiens 6-13 8384002-4 1993 In contrast, the activatory effect of insulin on System A was largely inhibited by phospholipase C. The effects of phospholipase C on transport processes differed from the effects provoked by phorbol esters (TPA), indicating that they are not just a consequence of TPA-sensitive protein kinase C activation. Phorbol Esters 192-206 insulin Homo sapiens 38-45 8382476-0 1993 Phorbol esters inhibit insulin-induced receptor down-regulation in cultured human lymphocytes: association with diminished insulin receptor autophosphorylation. Phorbol Esters 0-14 insulin Homo sapiens 23-30 1650476-8 1991 Thus, although it has been previously shown that insulin and phorbol esters repress PEPCK gene transcription through distinct pathways, the final target of insulin and phorbol ester action is the same DNA element. Phorbol Esters 61-74 insulin Homo sapiens 156-163 2018470-0 1991 Phorbol ester only partially mimics the effects of insulin on glucose transport and glucose-transporter distribution in 3T3-L1 adipocytes. Phorbol Esters 0-13 insulin Homo sapiens 51-58 2018470-5 1991 We suggest that the stimulation of transport by insulin and PMA occurs via different mechanisms, which is manifested by the ability of insulin to induce a much greater increase in the plasma-membrane content of GLUT 4 compared with the phorbol ester. Phorbol Esters 236-249 insulin Homo sapiens 48-55 2173567-3 1990 In order to determine whether phorbol esters might inhibit insulin signalling also at the level of a phospholipase C, we studied the insulin dependent [3H] phosphatidylinositol 4-monophosphate (PIP) hydrolysis of fat cell membranes. Phorbol Esters 30-44 insulin Homo sapiens 59-66 2207658-0 1990 Phorbol esters increase insulin binding in astrocytic glial but not neuronal cells in primary culture from the brain. Phorbol Esters 0-14 insulin Homo sapiens 24-31 2219271-5 1990 Cyclosporine also inhibits by 66% the insulin secretory response to 100 nmol/L phorbol 12-myristate 13-acetate, suggesting that either cyclosporine interferes with phorbol ester action on beta cells or the action site is located beyond the protein kinase C activation. Phorbol Esters 164-177 insulin Homo sapiens 38-45 2207658-1 1990 In this study we used differential culturing techniques to study the effects of phorbol esters on insulin receptors on neuronal and astrocytic glial cells in primary culture from the brain. Phorbol Esters 80-94 insulin Homo sapiens 98-105 2207658-4 1990 The TPA effect on glial [125I]insulin binding was specific as evidenced by the observation that potencies of phorbol ester analogs to increase [125I]insulin binding were similar to their abilities to stimulate PKC. Phorbol Esters 109-122 insulin Homo sapiens 30-37 2207658-4 1990 The TPA effect on glial [125I]insulin binding was specific as evidenced by the observation that potencies of phorbol ester analogs to increase [125I]insulin binding were similar to their abilities to stimulate PKC. Phorbol Esters 109-122 insulin Homo sapiens 149-156 2163613-9 1990 Furthermore, the effects of insulin and PMA on glucose consumption, lactate production, Fru-2,6-P2 levels and PFK2 activity are additive, and the effect of insulin on Fru-2,6-P2 production is not altered by pre-treatment of the cells with the phorbol ester. Phorbol Esters 243-256 insulin Homo sapiens 28-35 2690823-1 1989 The tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) induces insulin secretion from isolated pancreatic islets, and this suggests a potential role for protein kinase C in the regulation of stimulus-secretion coupling in islets. Phorbol Esters 21-34 insulin Homo sapiens 86-93 2557924-2 1989 p68 undergoes rapid, cation-independent phosphorylation in unstimulated membrane vesicles which was inhibited, in a dose-dependent manner, by insulin, platelet-derived growth factor, macrophage colony stimulating factor, protein kinase C-activating phorbol esters and phosphatidylinositol-specific phospholipase C. Epidermal growth factor had no effect on overall p68 phosphorylation. Phorbol Esters 249-263 insulin Homo sapiens 142-149 2110001-0 1990 Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase C. The ability of tumor-promoting phorbol diesters to inhibit both insulin receptor tyrosine kinase activity and its intracellular signaling correlates with the phosphorylation of the insulin receptor beta subunit on serine and threonine residues. Phorbol Esters 135-151 insulin Homo sapiens 28-35 2110001-0 1990 Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase C. The ability of tumor-promoting phorbol diesters to inhibit both insulin receptor tyrosine kinase activity and its intracellular signaling correlates with the phosphorylation of the insulin receptor beta subunit on serine and threonine residues. Phorbol Esters 135-151 insulin Homo sapiens 168-175 2803236-7 1989 Almost the full insulin effect was mimicked by a combination of phorbol esters and IP-oligosaccharides (basal 7%, insulin 50%, IP-oligosaccharides 30%, TPA 23%, IP-oligosaccharides + TPA 45%). Phorbol Esters 64-78 insulin Homo sapiens 16-23 2803236-7 1989 Almost the full insulin effect was mimicked by a combination of phorbol esters and IP-oligosaccharides (basal 7%, insulin 50%, IP-oligosaccharides 30%, TPA 23%, IP-oligosaccharides + TPA 45%). Phorbol Esters 64-78 insulin Homo sapiens 114-121 2547602-4 1989 These data not only demonstrate an insulin-like effect of phorbol esters in adipose tissue but they lend support to the concept of diacylglycerol involvement in the mechanism of insulin action. Phorbol Esters 58-72 insulin Homo sapiens 35-42 3276673-2 1988 Both insulin and the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) induced c-fos mRNA accumulation in cells expressing high numbers of normal human insulin receptors; PMA but not insulin was effective in the cells expressing the mutant receptor. Phorbol Esters 37-50 insulin Homo sapiens 170-177 2646943-8 1989 Measured either early or late after TPA addition, the phorbol ester reduced insulin binding by congruent to 40%. Phorbol Esters 54-67 insulin Homo sapiens 76-83