PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 34665880-4 2021 The fact that reduced function variants of the key transporter that takes metformin into the liver (OCT1) do not alter glycaemic response to metformin suggests that metformin does not need to get into the liver to work. Metformin 74-83 solute carrier family 22 member 1 Homo sapiens 100-104 34194474-9 2021 Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. Metformin 290-299 solute carrier family 22 member 1 Homo sapiens 40-68 34422646-2 2021 Metformin requires organic cation transporters (OCTs) for entry into cells, and NT-1044 is an AMPK activator designed to have greater affinity for two of these transporters, OCT1 and OCT3. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 174-178 34194474-9 2021 Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. Metformin 290-299 solute carrier family 22 member 1 Homo sapiens 70-75 34194474-9 2021 Carriers of reduced-function alleles of organic cation transporter 1 (OCT 1, encoded by SLC22A1) or reduced expression alleles of plasma membrane monoamine transporter (PMAT, encoded by SLC29A4) or serotonin transporter (SERT, encoded by SLC6A4) were associated with increased incidence of metformin-related gastrointestinal (GI) adverse effects. Metformin 290-299 solute carrier family 22 member 1 Homo sapiens 88-95 34064886-7 2021 Individual contributions of transporters to metformin disposition are renal OCT2 renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT. Metformin 44-53 solute carrier family 22 member 1 Homo sapiens 123-127 34064886-2 2021 Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Metformin 143-152 solute carrier family 22 member 1 Homo sapiens 8-12 34545025-0 2022 Association of SLC22A1 rs622342 and ATM rs11212617 polymorphisms with metformin efficacy in patients with type 2 diabetes. Metformin 70-79 solute carrier family 22 member 1 Homo sapiens 15-22 35619086-0 2022 Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes. Metformin 89-98 solute carrier family 22 member 1 Homo sapiens 14-42 35619086-0 2022 Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes. Metformin 89-98 solute carrier family 22 member 1 Homo sapiens 44-49 35619086-0 2022 Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes. Metformin 89-98 solute carrier family 22 member 1 Homo sapiens 50-57 35619086-1 2022 BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. Metformin 73-82 solute carrier family 22 member 1 Homo sapiens 12-40 35619086-3 2022 In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. Metformin 167-176 solute carrier family 22 member 1 Homo sapiens 86-90 35619086-4 2022 RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. Metformin 51-60 solute carrier family 22 member 1 Homo sapiens 157-162 35619086-6 2022 Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Metformin 93-102 solute carrier family 22 member 1 Homo sapiens 83-88 35619086-8 2022 The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. Metformin 205-214 solute carrier family 22 member 1 Homo sapiens 59-64 35619086-9 2022 CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders. Metformin 90-99 solute carrier family 22 member 1 Homo sapiens 64-69 35619086-9 2022 CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders. Metformin 178-187 solute carrier family 22 member 1 Homo sapiens 118-122 34545025-9 2022 Our results indicated that common variants of SLC22A1 rs622342 and ATM rs11212617 were associated with the efficacy of metformin in T2DM of Han nationality in Chaoshan China. Metformin 119-128 solute carrier family 22 member 1 Homo sapiens 46-53 33658930-9 2020 Metformin efficacy considerably varies from one patient to another; this may be largely attributed to the presence of mutations on the SLC22A1 gene. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 135-142 33967805-1 2021 Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine). Metformin 282-291 solute carrier family 22 member 1 Homo sapiens 0-28 33967805-1 2021 Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine). Metformin 282-291 solute carrier family 22 member 1 Homo sapiens 30-34 33967805-1 2021 Organic Cation Transporter 1 (OCT1, gene symbol: SLC22A1) is predominately expressed in human liver, localized in the basolateral membrane of hepatocytes and facilitates the uptake of endogenous compounds (e.g. serotonin, acetylcholine, thiamine), and widely prescribed drugs (e.g. metformin, fenoterol, morphine). Metformin 282-291 solute carrier family 22 member 1 Homo sapiens 49-56 33658930-10 2020 This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint. Metformin 62-71 solute carrier family 22 member 1 Homo sapiens 72-77 33658930-10 2020 This study aims at proposing a potential structural model for metformin-hOCT1 (SLC22A1) transporter interaction, as well as the identification of the effect of mutations G401S (rs34130495), S189L (rs34104736), and R206C (616C > T) of the SLC22A1 gene at the topological and electronic structure levels on the channel surfaces, from a chemical viewpoint. Metformin 62-71 solute carrier family 22 member 1 Homo sapiens 79-86 33037045-1 2020 The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1). Metformin 46-55 solute carrier family 22 member 1 Homo sapiens 105-109 33533444-0 2020 Assessment of Interaction of Human OCT 1-3 Proteins and Metformin Using Silico Analyses. Metformin 56-65 solute carrier family 22 member 1 Homo sapiens 35-42 33533444-1 2020 Metformin, a drug frequently used by diabetic patients as the first-line treatment worldwide, is positively charged and is transported into the cell through human organic cation transporter (hOCT 1-3) proteins. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 191-199 33533444-2 2020 We aimed to mimic the cellular uptake of metformin by hOCT1-3 with various bioinformatics methods and tools. Metformin 41-50 solute carrier family 22 member 1 Homo sapiens 54-61 33533444-6 2020 We simulated the OCT1-3 and metformin docking and also validated the docking procedure with other substrates of HOCT1-3 proteins. Metformin 28-37 solute carrier family 22 member 1 Homo sapiens 112-119 33037045-1 2020 The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1). Metformin 46-55 solute carrier family 22 member 1 Homo sapiens 111-118 33037045-10 2020 In conclusion, the contribution of human OCT1 to the cellular uptake of thiamine and especially of metformin may be much lower than that of mouse OCT1. Metformin 99-108 solute carrier family 22 member 1 Homo sapiens 41-45 33037045-13 2020 Significance Statement OCT1 is a major hepatic uptake transporter of metformin and thiamine, but we report strong differences in the affinity for both compounds between human and mouse OCT1. Metformin 69-78 solute carrier family 22 member 1 Homo sapiens 23-27 33037045-14 2020 Consequently, intrahepatic metformin concentrations could be much higher in mice than in humans, impacting metformin actions and representing a strong limitation of using rodent animal models for predictions of OCT1-related pharmacokinetics and efficacy in humans. Metformin 27-36 solute carrier family 22 member 1 Homo sapiens 211-215 33037045-15 2020 Furthermore, OCT1 transmembrane helices TMH2 and TMH3 were identified to confer the observed species-specific differences in metformin affinity. Metformin 125-134 solute carrier family 22 member 1 Homo sapiens 13-17 32843330-8 2020 Next, using the REF approach, we predicted the in vivo metformin CLh,s,in using OCT1-transporter expressing HEK293 cells or plated human hepatocytes. Metformin 55-64 solute carrier family 22 member 1 Homo sapiens 80-84 32843330-12 2020 Significance Statement This study is the first to use OCT1-expressing cells and plated hepatocytes to compare proteomics-informed REF approach with the traditional MGPGL approach to predict hepatic uptake CL of metformin in humans. Metformin 211-220 solute carrier family 22 member 1 Homo sapiens 54-58 32455555-4 2020 In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil. Metformin 11-20 solute carrier family 22 member 1 Homo sapiens 36-76 32551505-5 2020 The assay is capable of simultaneously quantifying multiple endogenous compounds, including IBC, thiamine, N1-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, a substrate for OCT1/2 and MATE1/2K in clinical studies. Metformin 165-174 solute carrier family 22 member 1 Homo sapiens 192-198 31883148-8 2020 Furthermore, transport of cationic drugs, metformin and paclitaxel in HepG2 cells was blunted by OCT inhibitors, suggesting that hOCT1 and hOCT3 expressed in HepG2 cells exhibit notable impacts on cationic drug actions. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 129-134 32472157-3 2020 Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K. Metformin 28-37 solute carrier family 22 member 1 Homo sapiens 53-81 32472157-3 2020 Hepatic and renal uptake of metformin is mediated by organic cation transporter 1 (OCT1) and OCT2, respectively, and its renal excretion by multidrug and toxin extrusion 1 (MATE1) and MATE2-K. Metformin 28-37 solute carrier family 22 member 1 Homo sapiens 83-87 32472157-5 2020 METHODS: Inhibitory effects of peficitinib and its metabolite H2 on metformin uptake into human OCT1/2- and MATE1/2-K-expressing cells were assessed in vitro. Metformin 68-77 solute carrier family 22 member 1 Homo sapiens 96-102 32472157-9 2020 RESULTS: Peficitinib, but not H2, inhibited metformin uptake into OCT1- and MATE1/2-K-expressing cells. Metformin 44-53 solute carrier family 22 member 1 Homo sapiens 66-70 32575674-0 2020 rs622342 in SLC22A1, CYP2C9*2 and CYP2C9*3 and Glycemic Response in Individuals with Type 2 Diabetes Mellitus Receiving Metformin/Sulfonylurea Combination Therapy: 6-Month Follow-Up Study. Metformin 120-129 solute carrier family 22 member 1 Homo sapiens 12-19 32575674-11 2020 CONCLUSION: The combination of metformin/sulfonylurea therapy led to the maximum glycemic control in individuals with T2DM carrying AA or AC genotypes in SLC22A1 and *1*3 in CYP2C9. Metformin 31-40 solute carrier family 22 member 1 Homo sapiens 154-161 32606866-0 2020 Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes. Metformin 88-97 solute carrier family 22 member 1 Homo sapiens 21-25 32606866-7 2020 Results: In a multivariate Cox regression analysis adjusted for classical cardiovascular risk factors, 4 intronic OCT1 SNPs were significantly associated with all-cause and cardiovascular mortality in individuals with T2DM on metformin therapy. Metformin 226-235 solute carrier family 22 member 1 Homo sapiens 114-118 32606866-8 2020 Conclusion: According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death. Metformin 76-85 solute carrier family 22 member 1 Homo sapiens 31-35 32455555-4 2020 In case of metformin and verapamil, organic cation transporter (OCT) 1 and 2 primarily mediate metformin distribution to the liver and its elimination into urine, whereas cytochrome P450 is responsible for the hepatic metabolism of verapamil. Metformin 95-104 solute carrier family 22 member 1 Homo sapiens 36-76 32127372-6 2020 Uptake of the OCT1 substrate metformin in SCHH was decreased by T0901317 treatment. Metformin 29-38 solute carrier family 22 member 1 Homo sapiens 14-18 32454819-0 2020 SLC22A1 rs622342 Polymorphism Predicts Insulin Resistance Improvement in Patients with Type 2 Diabetes Mellitus Treated with Metformin: A Cross-Sectional Study. Metformin 125-134 solute carrier family 22 member 1 Homo sapiens 0-7 32454819-2 2020 Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. Metformin 86-95 solute carrier family 22 member 1 Homo sapiens 0-28 32454819-2 2020 Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. Metformin 86-95 solute carrier family 22 member 1 Homo sapiens 41-48 32454819-3 2020 The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment. Metformin 213-222 solute carrier family 22 member 1 Homo sapiens 65-72 32127372-7 2020 Effects of decreased OCT1 levels on metformin were simulated using a physiologically-based pharmacokinetic (PBPK) model. Metformin 36-45 solute carrier family 22 member 1 Homo sapiens 21-25 31974043-0 2020 rs622342A>C in SLC22A1 is associated with metformin pharmacokinetics and glycemic response. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 15-22 31974043-1 2020 Polymorphisms in SLC22A1 lead to variability in metformin clinical efficacy. Metformin 48-57 solute carrier family 22 member 1 Homo sapiens 17-24 31974043-7 2020 The rs622342A>C in SLC22A1 may be associated with metformin pharmacokinetics and variability in therapeutic efficacy. Metformin 50-59 solute carrier family 22 member 1 Homo sapiens 19-26 31886264-3 2019 Metformin relies on organic cation transporters (OCT1), a polyspecific cell membrane of the solute carrier 22A (SLC22A) gene family, to facilitate its intracellular uptake and action on complex I of the respiratory chain of mitochondria. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 49-53 32407269-10 2020 CONCLUSION: The interaction between rs72552763 and rs622342 in OCT1, and rs12943590 in MATE2 suggested an important role of these polymorphisms in metformin response in T2D Mexican Mestizo population. Metformin 147-156 solute carrier family 22 member 1 Homo sapiens 63-67 31427432-3 2019 Following a 30 minute preincubation with an inhibitor, approximately 50-fold higher inhibition potency was observed for Cyclosporine (CsA) against OCT1-mediated uptake of metformin as compared to coincubation, with IC50 values of 0.43 +- 0.12 and 21.6 +- 4.5 muM, respectively. Metformin 171-180 solute carrier family 22 member 1 Homo sapiens 147-151 31427432-8 2019 A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer. Metformin 123-132 solute carrier family 22 member 1 Homo sapiens 99-103 31427432-8 2019 A short (30 min) exposure to 10 muM CsA produced long-lasting (at least 120 min) inhibition of the OCT1-mediated uptake of metformin in OCT1-HEK293 cells, which was likely attributable to the retention of CsA in the cells, as shown by the fact that inhibitory cellular concentrations of CsA are maintained long after the removal of the compound from incubation buffer. Metformin 123-132 solute carrier family 22 member 1 Homo sapiens 136-140 31427432-12 2019 For the first time, we observed a 50-fold increase in CsA inhibitory potency against OCT1-mediated transport of metformin following a preincubation step. Metformin 112-121 solute carrier family 22 member 1 Homo sapiens 85-89 30885951-0 2019 Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study. Metformin 180-189 solute carrier family 22 member 1 Homo sapiens 87-115 31012983-0 2019 Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study. Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 62-69 31012983-0 2019 Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study. Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 71-75 31012983-1 2019 The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. Metformin 207-216 solute carrier family 22 member 1 Homo sapiens 32-36 31012983-1 2019 The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. Metformin 207-216 solute carrier family 22 member 1 Homo sapiens 118-125 31012983-2 2019 The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. Metformin 156-165 solute carrier family 22 member 1 Homo sapiens 72-79 31188026-6 2019 Results: In the primary analysis, both ATM and OCT1 showed significant effects of genotype on change in body mass index z-scores, the primary outcome measure, during the first 16 weeks of treatment with metformin. Metformin 203-212 solute carrier family 22 member 1 Homo sapiens 47-51 31231590-3 2019 Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Metformin 80-89 solute carrier family 22 member 1 Homo sapiens 39-46 31231590-3 2019 Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Metformin 128-137 solute carrier family 22 member 1 Homo sapiens 39-46 31231590-11 2019 Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112-6.385). Metformin 162-171 solute carrier family 22 member 1 Homo sapiens 5-12 30975793-8 2019 OCT1-mediated uptake was prominent for class 2/4 compounds (e.g., metformin). Metformin 66-75 solute carrier family 22 member 1 Homo sapiens 0-4 30885951-0 2019 Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study. Metformin 180-189 solute carrier family 22 member 1 Homo sapiens 117-121 30885951-3 2019 We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 109-137 30885951-3 2019 We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 139-143 30959948-0 2019 Association between Polymorphisms of OCT1 and Metabolic Response to Metformin in Women with Polycystic Ovary Syndrome. Metformin 68-77 solute carrier family 22 member 1 Homo sapiens 37-41 30959948-3 2019 Organic cation transporter (OCT) 1 and 2 have been reported to mediate metformin transport in the liver and kidney, respectively. Metformin 71-80 solute carrier family 22 member 1 Homo sapiens 0-40 30959948-4 2019 In this study, we investigated the association between the polymorphisms of OCT1 and OCT2 and the treatment effectiveness of metformin in PCOS patients. Metformin 125-134 solute carrier family 22 member 1 Homo sapiens 76-80 30959948-8 2019 However, PCOS patients with the G allele of OCT1 rs683369 and/or with the A allele of OCT1 rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment. Metformin 192-201 solute carrier family 22 member 1 Homo sapiens 86-90 30959948-9 2019 Moreover, the interactions of metformin*SNP were significant in both OCT1 rs683369 (p < 0.001) and rs628031 (p = 0.001) during the treatment period. Metformin 30-39 solute carrier family 22 member 1 Homo sapiens 69-73 30959948-10 2019 Taken together, genetic polymorphisms of OCT1 contributed to different metformin treatment responses, and further study is needed to establish personalized treatment programs using a pharmacogenomic algorithm approach in PCOS patients. Metformin 71-80 solute carrier family 22 member 1 Homo sapiens 41-45 30041690-0 2018 Genetic polymorphisms of organic cation transporters 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes mellitus: a systematic review protocol. Metformin 79-88 solute carrier family 22 member 1 Homo sapiens 25-54 30934600-0 2019 Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 39-46 30934600-3 2019 The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Metformin 186-195 solute carrier family 22 member 1 Homo sapiens 129-136 31804919-4 2019 METHODS: Rosuvastatin, digoxin, and metformin were selected as probe substrates of hepatic transporters OATP1B1, OATP1B3, BCRP, P-gp, and OCT1. Metformin 36-45 solute carrier family 22 member 1 Homo sapiens 138-142 30375241-5 2018 The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Metformin 119-128 solute carrier family 22 member 1 Homo sapiens 193-200 30375241-6 2018 Expert opinion: Candidate gene studies have shown that genetic variations in SLC22A1 and other drug transporters influence the pharmacokinetics, glycemic responses, and gastrointestinal intolerance to metformin, although results are somewhat discordant. Metformin 201-210 solute carrier family 22 member 1 Homo sapiens 77-84 30138624-2 2018 The substrates and inhibitors of hOCT1 are structurally and physiochemically diverse and include some widely prescribed drugs (metformin and imatinib), vitamins (thiamine), and neurotransmitters (serotonin). Metformin 127-136 solute carrier family 22 member 1 Homo sapiens 33-38 30191328-3 2018 METHODS: The inhibition by select compounds on the uptake of the probe substrate metformin was assessed in HEK293 cells overexpressing human OCT2, OCT1, MATE1, MATE2-K, and mouse Oct2, Oct1, and Mate1. Metformin 81-90 solute carrier family 22 member 1 Homo sapiens 147-151 30834005-2 2019 Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal. Metformin 115-124 solute carrier family 22 member 1 Homo sapiens 0-34 30834005-2 2019 Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal. Metformin 115-124 solute carrier family 22 member 1 Homo sapiens 58-65 30834005-2 2019 Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal. Metformin 204-213 solute carrier family 22 member 1 Homo sapiens 0-34 30834005-2 2019 Organic Cation Transporter (OCT) 1 protein encoded by the SLC22A1 gene is primarily responsible for the process of metformin influx to the hepatocytes as the target of antihyperglycemic action as well as metformin elimination through the renal. Metformin 204-213 solute carrier family 22 member 1 Homo sapiens 58-65 30544975-1 2018 The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine. Metformin 152-161 solute carrier family 22 member 1 Homo sapiens 4-32 30544975-1 2018 The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine. Metformin 152-161 solute carrier family 22 member 1 Homo sapiens 34-38 30544975-1 2018 The organic cation transporter 1 (OCT1, SLC22A1) is strongly expressed in the human liver and facilitates the hepatic uptake of drugs such as morphine, metformin, tropisetron, sumatriptan and fenoterol and of endogenous substances such as thiamine. Metformin 152-161 solute carrier family 22 member 1 Homo sapiens 40-47 30294927-4 2018 The data demonstrated that nuciferine significantly reduced metformin accumulation in MDCK cells stably expressing human OCT1 (MDCK-hOCT1) or hMATE1 (MDCK-hMATE1), and primary cultured mouse hepatocytes. Metformin 60-69 solute carrier family 22 member 1 Homo sapiens 121-125 30294927-5 2018 Furthermore, the presence of nuciferine in the basal compartment caused a concentration-dependent reduction of intracellular metformin accumulation in MDCK-hOCT1/hMATE1 cell monolayers. Metformin 125-134 solute carrier family 22 member 1 Homo sapiens 156-161 30375241-5 2018 The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Metformin 119-128 solute carrier family 22 member 1 Homo sapiens 152-180 30375241-5 2018 The transporter variants identified to have an important influence on the absorption, distribution, and elimination of metformin, particularly those in organic cation transporter 1 (OCT1, gene SLC22A1), are reviewed. Metformin 119-128 solute carrier family 22 member 1 Homo sapiens 182-186 30041690-0 2018 Genetic polymorphisms of organic cation transporters 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes mellitus: a systematic review protocol. Metformin 79-88 solute carrier family 22 member 1 Homo sapiens 56-60 30041690-3 2018 This systematic review aims to highlight and summarize the overall effects of OCT1 polymorphisms on therapeutic responses to metformin and to evaluate their potential role in terms of interethnic differences with metformin responses. Metformin 125-134 solute carrier family 22 member 1 Homo sapiens 78-82 30041690-4 2018 METHODS/DESIGN: We will systematically review observational studies reporting on the genetic association between OCT1 polymorphisms and metformin responses in T2DM patients. Metformin 136-145 solute carrier family 22 member 1 Homo sapiens 113-117 30041690-11 2018 DISCUSSION: This review will summarize the genetic effects of OCT1 polymorphisms associated with variabilities in glycemic responses to metformin. Metformin 136-145 solute carrier family 22 member 1 Homo sapiens 62-66 29979413-0 2018 Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review. Metformin 78-87 solute carrier family 22 member 1 Homo sapiens 25-53 29979413-15 2018 CONCLUSION: Genetic effects of OCT1 polymorphisms on metformin responses were population specific. Metformin 53-62 solute carrier family 22 member 1 Homo sapiens 31-35 29979413-0 2018 Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes: A systematic review. Metformin 78-87 solute carrier family 22 member 1 Homo sapiens 55-59 29979413-5 2018 AIM: This study aims to highlight and summarize the overall effects of organic cation transporter 1(OCT1) polymorphisms on therapeutic responses to metformin and to evaluate the potential role of such polymorphisms in interethnic differences in metformin therapy. Metformin 148-157 solute carrier family 22 member 1 Homo sapiens 71-104 29979413-7 2018 We searched for PubMed/MEDLINE, Embase, and CINAHL, relevant studies reporting the effects of OCT1 polymorphisms on metformin therapy in T2DM individuals. Metformin 116-125 solute carrier family 22 member 1 Homo sapiens 94-98 29352482-6 2018 Multivariate modelling revealed that metformin AUC0-48h increased with age, food and carriage of rs12208357 in SLC22A1 but was inversely associated with body surface area and individual proportions of African ancestry. Metformin 37-46 solute carrier family 22 member 1 Homo sapiens 111-118 29352482-7 2018 CONCLUSIONS: A pharmacogenetic marker in OCT1 (SLC22A1 rs12208357), combined with demographic covariates (age, body surface area and individual proportion of African ancestry) and a food effect explained 29.7% of the variability in metformin AUC0-48h . Metformin 232-241 solute carrier family 22 member 1 Homo sapiens 47-54 29193038-3 2018 OCT1 mediates metformin distribution to the liver (key biophase). Metformin 14-23 solute carrier family 22 member 1 Homo sapiens 0-4 29193038-4 2018 As OCT1 modulation impacts metformin response, but not pharmacokinetics (PK), metformin DDI studies require pharmacodynamic endpoint(s) to inform rational metformin dose adjustment. Metformin 27-36 solute carrier family 22 member 1 Homo sapiens 3-7 28494141-5 2018 Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin. Metformin 187-196 solute carrier family 22 member 1 Homo sapiens 83-111 29306537-11 2018 The Western blot assay showed that DPCs express functional organic cation transporter 1, a transmembrane protein that mediates the intracellular uptake of metformin. Metformin 155-164 solute carrier family 22 member 1 Homo sapiens 59-87 28494141-5 2018 Immunoblotting and cellular uptake assays showed that iPSC-MSCs express functional organic cation transporter-1 (OCT-1), a transmembrane protein that mediates the intracellular uptake of metformin. Metformin 187-196 solute carrier family 22 member 1 Homo sapiens 113-118 29236753-14 2017 Ranitidine inhibited the OCT1-mediated uptake of metformin and morphine at clinically relevant concentrations. Metformin 49-58 solute carrier family 22 member 1 Homo sapiens 25-29 29949790-0 2018 OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity. Metformin 14-23 solute carrier family 22 member 1 Homo sapiens 0-4 29949790-10 2018 Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. Metformin 265-274 solute carrier family 22 member 1 Homo sapiens 132-167 29949790-10 2018 Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. Metformin 265-274 solute carrier family 22 member 1 Homo sapiens 169-173 29949790-10 2018 Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. Metformin 265-274 solute carrier family 22 member 1 Homo sapiens 132-167 29949790-10 2018 Adenosine monophosphate-activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. Metformin 265-274 solute carrier family 22 member 1 Homo sapiens 169-173 29949790-12 2018 Silencing of OCT1 expression resulted in a reduction in the effects of metformin on PSCs activity. Metformin 71-80 solute carrier family 22 member 1 Homo sapiens 13-17 29949790-13 2018 CONCLUSIONS: Collectively, the data indicate that OCT1 may contribute to uptake metformin and regulate PSCs activity. Metformin 80-89 solute carrier family 22 member 1 Homo sapiens 50-54 29949790-14 2018 OCT1 is a target of metformin in regulating PSCs activity. Metformin 20-29 solute carrier family 22 member 1 Homo sapiens 0-4 29089306-9 2018 Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1. Metformin 62-71 solute carrier family 22 member 1 Homo sapiens 13-17 29089306-9 2018 Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1. Metformin 62-71 solute carrier family 22 member 1 Homo sapiens 47-51 29089306-9 2018 Importantly, OCT1-mediated uptake of a typical OCT1 substrate metformin was inhibited by pazopanib with an IC50 value of 0.253 microM, indicating that pazopanib has the potential for clinically relevant inhibition of human OCT1. Metformin 62-71 solute carrier family 22 member 1 Homo sapiens 47-51 27493135-7 2016 In the analyses stratified by SERT genotype, the presence of two deficient OCT1 alleles was associated with more than a ninefold higher odds of metformin intolerance in patients carrying the L*L* genotype (OR 9.25 [95% CI 3.18-27.0], P < 10-4); however, it showed a much smaller effect in L*S* carriers and no effect in S*S* carriers. Metformin 144-153 solute carrier family 22 member 1 Homo sapiens 75-79 28380657-0 2017 Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans. Metformin 73-82 solute carrier family 22 member 1 Homo sapiens 25-53 28380657-3 2017 The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. Metformin 147-156 solute carrier family 22 member 1 Homo sapiens 64-71 28380657-3 2017 The aim of this study was to examine if common polymorphisms in SLC22A1, encoding the transporter protein OCT1, affect the hepatic distribution of metformin in humans. Metformin 147-156 solute carrier family 22 member 1 Homo sapiens 106-110 28380657-5 2017 Hepatic distribution of metformin was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Metformin 24-33 solute carrier family 22 member 1 Homo sapiens 122-129 28947922-6 2017 Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication. Metformin 122-131 solute carrier family 22 member 1 Homo sapiens 46-53 28947922-6 2017 Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication. Metformin 173-182 solute carrier family 22 member 1 Homo sapiens 46-53 28947922-9 2017 Importantly, metformin treatment did also directly decrease DNA methylation of SLC22A1 in hepatocytes cultured in vitro. Metformin 13-22 solute carrier family 22 member 1 Homo sapiens 79-86 27407018-0 2017 Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance. Metformin 36-45 solute carrier family 22 member 1 Homo sapiens 11-18 27407018-0 2017 Effects of SLC22A1 Polymorphisms on Metformin-Induced Reductions in Adiposity and Metformin Pharmacokinetics in Obese Children With Insulin Resistance. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 11-18 27407018-7 2017 However, SLC22A1 variant carriers had smaller reductions in percentage of total trunk fat after metformin therapy, although the percentage reduction in trunk fat was small. Metformin 96-105 solute carrier family 22 member 1 Homo sapiens 9-16 27407018-9 2017 Future study is needed to evaluate the effects of SLC22A1 polymorphisms on metformin-mediated weight reduction in obese children. Metformin 75-84 solute carrier family 22 member 1 Homo sapiens 50-57 27493135-2 2016 We have previously shown that reduced-function alleles of organic cation transporter 1 (OCT1) are associated with increased intolerance to metformin. Metformin 139-148 solute carrier family 22 member 1 Homo sapiens 58-86 27493135-2 2016 We have previously shown that reduced-function alleles of organic cation transporter 1 (OCT1) are associated with increased intolerance to metformin. Metformin 139-148 solute carrier family 22 member 1 Homo sapiens 88-92 27493135-8 2016 CONCLUSIONS: Our results indicate that the interaction between OCT1 and SERT genes might play an important role in metformin intolerance. Metformin 115-124 solute carrier family 22 member 1 Homo sapiens 63-67 27128732-4 2016 Increased odds ratio of early discontinuation of metformin was only associated with codeine, an inhibitor of organic cation transporter 1 in both cohorts [adjusted odds ratio (OR) in Danish cohort (95% CI): 1.13 (1.02-1.26), adjusted OR in American cohort (95% CI): 1.32 (1.19-1.47)]. Metformin 49-58 solute carrier family 22 member 1 Homo sapiens 109-137 27317943-6 2016 Specifically, OCT1-mediated metformin access to its site of action in the liver is impacted by genetic polymorphisms and chemical inhibition of OCT1. Metformin 28-37 solute carrier family 22 member 1 Homo sapiens 14-18 27317943-6 2016 Specifically, OCT1-mediated metformin access to its site of action in the liver is impacted by genetic polymorphisms and chemical inhibition of OCT1. Metformin 28-37 solute carrier family 22 member 1 Homo sapiens 144-148 27555891-7 2016 Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. Metformin 310-319 solute carrier family 22 member 1 Homo sapiens 208-215 27019345-4 2016 The models were used to simulate inhibition of the MATE1, MATE2-K, OCT1 and OCT2 mediated transport of metformin by cimetidine. Metformin 103-112 solute carrier family 22 member 1 Homo sapiens 67-71 27019345-7 2016 An alternative description of metformin renal transport by OCT1 and OCT2, incorporating electrochemical modulation of the rate of metformin uptake together with 8-18-fold decreases in cimetidine Ki"s for OCTs and MATEs, allowed recovery of the extent of the observed effect of cimetidine on metformin AUC. Metformin 30-39 solute carrier family 22 member 1 Homo sapiens 59-63 26605869-3 2016 We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. Metformin 118-127 solute carrier family 22 member 1 Homo sapiens 47-75 26605869-3 2016 We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. Metformin 118-127 solute carrier family 22 member 1 Homo sapiens 77-81 26605869-4 2016 The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. Metformin 104-113 solute carrier family 22 member 1 Homo sapiens 56-60 26605869-9 2016 Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034). Metformin 133-142 solute carrier family 22 member 1 Homo sapiens 29-33 26605869-10 2016 CONCLUSIONS: In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. Metformin 106-115 solute carrier family 22 member 1 Homo sapiens 81-85 26605869-11 2016 These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. Metformin 76-85 solute carrier family 22 member 1 Homo sapiens 61-65 27386433-0 2016 Impact of ATM and SLC22A1 Polymorphisms on Therapeutic Response to Metformin in Iranian Diabetic Patients. Metformin 67-76 solute carrier family 22 member 1 Homo sapiens 18-25 26700958-6 2016 After incubation of the cells with 5 microM metformin, the intracellular concentrations were 26.4 +- 7.8 muM and 268 +- 11.0 muM, respectively, in HEK-EV and HEK-OCT1. Metformin 44-53 solute carrier family 22 member 1 Homo sapiens 162-166 26700958-7 2016 In addition, intracellular metformin concentrations were lower in high K(+) buffer (140 mM KCl) compared with normal K(+) buffer (5.4 mM KCl) in HEK-OCT1 cells (54.8 +- 3.8 muM and 198.1 +- 11.2 muM, respectively; P < 0.05). Metformin 27-36 solute carrier family 22 member 1 Homo sapiens 149-153 26977146-8 2016 After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p = 0.015) and decrease in HOMA-IS (p = 0.001) and QUICKI (p = 0.002) than A allele carriers. Metformin 6-15 solute carrier family 22 member 1 Homo sapiens 27-34 26977146-13 2016 Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients. Metformin 89-98 solute carrier family 22 member 1 Homo sapiens 22-29 26526073-6 2015 A paradigm in the field of drug transporter pharmacogenetics is the impact of hOCT1 gene variability on metformin clinical parameters, affecting area under the concentration-time curve, Cmax and responsiveness. Metformin 104-113 solute carrier family 22 member 1 Homo sapiens 78-83 26528626-3 2015 Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. Metformin 120-129 solute carrier family 22 member 1 Homo sapiens 43-71 26528626-3 2015 Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. Metformin 120-129 solute carrier family 22 member 1 Homo sapiens 73-77 25492374-0 2015 Influence of SLC22A1 rs622342 genetic polymorphism on metformin response in South Indian type 2 diabetes mellitus patients. Metformin 54-63 solute carrier family 22 member 1 Homo sapiens 13-20 25492374-3 2015 It has been hypothesized that genetic variations of SLC22A1 gene will influence inter-individual variation in glucose lowering efficacy of metformin. Metformin 139-148 solute carrier family 22 member 1 Homo sapiens 52-59 25492374-5 2015 Henceforth, the objective of the study was to evaluate the impact of SLC22A1 rs622342 gene polymorphism on the clinical efficacy of metformin in South Indian T2DM patients. Metformin 132-141 solute carrier family 22 member 1 Homo sapiens 69-76 25492374-17 2015 These data suggest that the allele and genotypes of SLC22A1 rs622342 gene polymorphism were associated with the therapeutic efficacy of metformin in South Indian patients with T2DM. Metformin 136-145 solute carrier family 22 member 1 Homo sapiens 52-59 26335661-4 2015 Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 54-58 26335661-4 2015 Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 107-111 25939711-1 2015 PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1). Metformin 84-93 solute carrier family 22 member 1 Homo sapiens 174-202 26426900-5 2015 OCT1-, OCT2-, MATE1- and MATE2-K-mediated metformin uptake was significantly reduced in the presence of green tea and EGCG (P < 0.05). Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 0-4 26464716-0 2015 Genetic variants of OCT1 influence glycemic response to metformin in Han Chinese patients with type-2 diabetes mellitus in Shanghai. Metformin 56-65 solute carrier family 22 member 1 Homo sapiens 20-24 26464716-1 2015 AIMS/HYPOTHESIS: Genetic variation in OCT1 can influence the glycemic response to metformin. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 38-42 26464716-2 2015 We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients. Metformin 127-136 solute carrier family 22 member 1 Homo sapiens 32-36 26464716-7 2015 Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA1c in HCS DM patients in response to metformin treatment. Metformin 172-181 solute carrier family 22 member 1 Homo sapiens 87-91 25939711-1 2015 PURPOSE: The aim of the study was to determine the steady-state pharmacokinetics of metformin in healthy volunteers with different numbers of reduced-function alleles in the organic cation transporter 1 gene (OCT1). Metformin 84-93 solute carrier family 22 member 1 Homo sapiens 209-213 25753371-0 2015 Multidrug and toxin extrusion 1 and human organic cation transporter 1 polymorphisms in patients with castration-resistant prostate cancer receiving metformin (SAKK 08/09). Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 42-70 25753371-1 2015 BACKGROUND: This study was initiated to explore the impact of organic cation transporter 1 (OCT1) and multidrug and toxin extrusion transporter 1 (MATE1) genetic polymorphisms on toxicity, and clinical activity of metformin in patients with castration-resistant prostate cancer (CRPC). Metformin 214-223 solute carrier family 22 member 1 Homo sapiens 62-90 25753371-11 2015 CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with less metformin-related toxicity and a higher risk of tumor progression in patients with CRPC receiving metformin as an anticancer treatment. Metformin 85-94 solute carrier family 22 member 1 Homo sapiens 29-33 25753371-11 2015 CONCLUSIONS: The polymorphic OCT1 C-allele has been shown to be associated with less metformin-related toxicity and a higher risk of tumor progression in patients with CRPC receiving metformin as an anticancer treatment. Metformin 183-192 solute carrier family 22 member 1 Homo sapiens 29-33 25359200-4 2015 To investigate whether this inhibitory effect of berberine on OCT1 and OCT2 could change the pharmacokinetics of metformin in vivo, we measured the effect of berberine co-administration on the pharmacokinetics of metformin at a single intravenous dose of 2 mg/kg metformin and 10 mg/kg berberine. Metformin 113-122 solute carrier family 22 member 1 Homo sapiens 62-66 25510240-0 2015 Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. Metformin 64-73 solute carrier family 22 member 1 Homo sapiens 15-43 25510240-3 2015 We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 56-84 25510240-3 2015 We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 86-90 25510240-3 2015 We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation. Metformin 107-116 solute carrier family 22 member 1 Homo sapiens 56-84 25510240-3 2015 We hypothesized that reduced transport of metformin via organic cation transporter 1 (OCT1) could increase metformin concentration in the intestine, leading to increased risk of severe GI side effects and drug discontinuation. Metformin 107-116 solute carrier family 22 member 1 Homo sapiens 86-90 25510240-8 2015 Our results suggest that reduced OCT1 transport is an important determinant of metformin intolerance. Metformin 79-88 solute carrier family 22 member 1 Homo sapiens 33-37 25199921-2 2015 A recent in vitro study found that proton pump inhibitors (PPIs) inhibit OCT1, OCT2 and OCT3, suggesting that PPIs might reduce metformin"s effectiveness. Metformin 128-137 solute carrier family 22 member 1 Homo sapiens 73-77 25359200-5 2015 In HEK293 cells, berberine inhibited OCT1- and OCT2-mediated metformin uptake in a concentration dependent manner and IC50 values for OCT1 and OCT2 were 7.28 and 11.3 muM, respectively. Metformin 61-70 solute carrier family 22 member 1 Homo sapiens 37-41 23922447-11 2013 It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin. Metformin 238-247 solute carrier family 22 member 1 Homo sapiens 157-161 25060604-1 2014 AIM: The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect. Metformin 91-100 solute carrier family 22 member 1 Homo sapiens 9-37 25060604-1 2014 AIM: The organic cation transporter 1 (OCT1) plays a key role in the cellular transport of metformin and its subsequent glucose-lowering effect. Metformin 91-100 solute carrier family 22 member 1 Homo sapiens 39-43 25060604-2 2014 A recent non-clinical study reported that metformin uptake into hepatocytes is regulated via OCT1, and that uptake was strongly inhibited by verapamil. Metformin 42-51 solute carrier family 22 member 1 Homo sapiens 93-97 25060604-7 2014 CONCLUSIONS: Our results suggest that verapamil remarkably decreases the glucose-lowering effect of metformin, possibly by acting as a competitive inhibitor of OCT1. Metformin 100-109 solute carrier family 22 member 1 Homo sapiens 160-164 25106415-6 2014 In contrast, uptake of the positive controls, atorvastatin for OATPs and metformin for OCT1, was significantly enhanced by relevant transporter expression, and uptake into both these HEK293 cells and human hepatocytes was significantly impaired by prototypical inhibitors. Metformin 73-82 solute carrier family 22 member 1 Homo sapiens 87-91 24145224-6 2013 The leading metformin response S-marker in combined group of DM2 patients was the CC variant of OCT1-R61C polymorphism of organic cation transporter protein 1 gene. Metformin 12-21 solute carrier family 22 member 1 Homo sapiens 96-100 23873119-1 2013 OBJECTIVE: The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T>C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes. Metformin 109-118 solute carrier family 22 member 1 Homo sapiens 369-373 22882994-2 2013 The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. Metformin 254-263 solute carrier family 22 member 1 Homo sapiens 169-176 23417334-1 2013 This study investigated the effects of genetic polymorphisms in organic cation transporter (OCT) genes, such as OCT1-3, OCTN1, MATE1, and MATE2-K, on metformin pharmacokinetics. Metformin 150-159 solute carrier family 22 member 1 Homo sapiens 112-118 22861817-3 2013 As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin. Metformin 129-138 solute carrier family 22 member 1 Homo sapiens 96-101 22861817-3 2013 As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin. Metformin 239-248 solute carrier family 22 member 1 Homo sapiens 96-101 22394605-1 2012 Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes. Metformin 294-303 solute carrier family 22 member 1 Homo sapiens 112-140 24324494-5 2013 SLC22A1, SLC47A1, and ATM gene variants were repeatedly associated with the response to metformin. Metformin 88-97 solute carrier family 22 member 1 Homo sapiens 0-7 24399729-1 2013 BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 12-40 24399729-1 2013 BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 42-46 24399729-1 2013 BACKGROUND: Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Metformin 149-158 solute carrier family 22 member 1 Homo sapiens 48-55 23984399-2 2013 Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Metformin 190-199 solute carrier family 22 member 1 Homo sapiens 24-31 23984399-2 2013 Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Metformin 190-199 solute carrier family 22 member 1 Homo sapiens 51-84 23984399-2 2013 Thus, downregulation of SLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Metformin 190-199 solute carrier family 22 member 1 Homo sapiens 86-90 22735389-0 2012 Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients. Metformin 197-206 solute carrier family 22 member 1 Homo sapiens 68-72 22735389-2 2012 So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. Metformin 185-194 solute carrier family 22 member 1 Homo sapiens 39-46 22735389-2 2012 So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. Metformin 185-194 solute carrier family 22 member 1 Homo sapiens 86-114 22735389-2 2012 So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. Metformin 185-194 solute carrier family 22 member 1 Homo sapiens 116-120 22735389-7 2012 CONCLUSION: Two genetic variations in OCT1 that are in strong linkage disequilibrium may predispose toward an increased prevalence of the side effects of metformin in patients with T2D. Metformin 154-163 solute carrier family 22 member 1 Homo sapiens 38-42 22394605-1 2012 Members of the human SLC superfamily such as organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, and organic cation transporter 1 (OCT1) are drug uptake transporters that are localised on the basolateral membrane of hepatocytes mediating the uptake of drugs such as atorvastatin and metformin into hepatocytes. Metformin 294-303 solute carrier family 22 member 1 Homo sapiens 142-146 22415520-5 2012 When comparing various substrates such as MPP+, TEA, metformin and lamivudine, the effects of the OCT1 genetic polymorphisms on their uptake were not identical. Metformin 53-62 solute carrier family 22 member 1 Homo sapiens 98-102 22415520-7 2012 In conclusion, the effect of genetic variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine was substrate-dependent. Metformin 93-102 solute carrier family 22 member 1 Homo sapiens 51-55 21989078-1 2011 OBJECTIVE: The aim of this study was to evaluate the effect of genetic variations in OCT1, OCT2, MATE1, MATE 2, and PMAT on the trough steady-state plasma concentration of metformin and hemoglobin A1c (Hb1Ac). Metformin 172-181 solute carrier family 22 member 1 Homo sapiens 85-89 22038047-7 2012 Prolonged metformin treatment in Calu-6 cells induced a dose-dependent expression increase of Cav-1 and OCT1, a metformin transporter. Metformin 10-19 solute carrier family 22 member 1 Homo sapiens 104-108 22038047-8 2012 Cav-1 and OCT1 expression was associated with the antiproliferative effect of metformin in Calu-6 cells (IC(50)=18 mM). Metformin 78-87 solute carrier family 22 member 1 Homo sapiens 10-14 21989078-4 2011 RESULTS: The mean trough steady-state metformin plasma concentration was estimated to be 576 ng/ml (range, 54-4133 ng/ml, p = 0.55) and correlated to the number of reduced function alleles in OCT1 (none, one or two: 642, 542, 397 ng/ml; P = 0.001). Metformin 38-47 solute carrier family 22 member 1 Homo sapiens 192-196 21989078-5 2011 The absolute decrease in Hb1Ac both initially and long term was also correlated to the number of reduced function alleles in OCT1 resulting in diminished pharmacodynamic effect of metformin after 6 and 24 months. Metformin 180-189 solute carrier family 22 member 1 Homo sapiens 125-129 21989078-6 2011 CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment. Metformin 158-167 solute carrier family 22 member 1 Homo sapiens 265-269 21989078-6 2011 CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment. Metformin 216-225 solute carrier family 22 member 1 Homo sapiens 194-198 21989078-6 2011 CONCLUSION: In a large cohort of type 2 diabetics, we either confirm or show for the first time: (a) an enormous (80-fold) variability in trough steady-state metformin plasma concentration, (b) OCT1 activity affects metformin steady-state pharmacokinetics, and (c) OCT1 genotype has a bearing on HbA1c during metformin treatment. Metformin 216-225 solute carrier family 22 member 1 Homo sapiens 194-198 21575951-1 2011 OBJECTIVE: To study the relationship between the responsiveness to metformin in girls with androgen excess and combinations of genetic variants-as reflected in a polymorphism score-in single nucleotide polymorphisms (OCT1, STK11, and FTO genes) and in the repeat numbers within the AR and SHBG genes. Metformin 67-76 solute carrier family 22 member 1 Homo sapiens 217-221 20567254-0 2011 Genotype-dependent effects of inhibitors of the organic cation transporter, OCT1: predictions of metformin interactions. Metformin 97-106 solute carrier family 22 member 1 Homo sapiens 76-80 20567254-1 2011 Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin. Metformin 174-183 solute carrier family 22 member 1 Homo sapiens 52-80 20567254-1 2011 Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin. Metformin 174-183 solute carrier family 22 member 1 Homo sapiens 82-86 20567254-1 2011 Common genetic variants of the liver-specific human organic cation transporter 1 (OCT1; SLC22A1) have reduced transport capacity for substrates such as the antidiabetic drug metformin. Metformin 174-183 solute carrier family 22 member 1 Homo sapiens 88-95 20567254-4 2011 In the second part OCT1-mediated (14)C-metformin uptake was studied in the presence of drugs administered concomitantly with metformin. Metformin 39-48 solute carrier family 22 member 1 Homo sapiens 19-23 20567254-8 2011 Concomitantly administered drugs, such as verapamil and amitriptyline, revealed potential drug-drug interactions at clinical plasma concentrations of metformin for OCT1-M420del. Metformin 150-159 solute carrier family 22 member 1 Homo sapiens 164-168 21986525-3 2011 The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. Metformin 97-106 solute carrier family 22 member 1 Homo sapiens 4-32 21986525-3 2011 The organic cation transporter 1 (OCT1) is known to play an important role in cellular uptake of metformin in the liver. Metformin 97-106 solute carrier family 22 member 1 Homo sapiens 34-38 21986525-4 2011 We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation. Metformin 95-104 solute carrier family 22 member 1 Homo sapiens 32-36 22345987-1 2011 BACKGROUND: Genetic variants of the organic cation transporter (OCT1) gene could influence interindividual variation in clinical response to metformin therapy. Metformin 141-150 solute carrier family 22 member 1 Homo sapiens 64-68 22345987-10 2011 The data observed in this study would justify further pharmacogenetic studies to potentially evaluate the role of OCT1 gene polymorphism in the therapeutic efficacy of metformin. Metformin 168-177 solute carrier family 22 member 1 Homo sapiens 114-118 20680652-1 2011 Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 19-47 21241070-17 2011 However, intersubject differences in the levels of expression of OCT1 and OCT3 in the liver are very large and may contribute more to the variations in the hepatic uptake and clinical effect of metformin. Metformin 194-203 solute carrier family 22 member 1 Homo sapiens 65-69 21677353-8 2011 Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively. Metformin 9-18 solute carrier family 22 member 1 Homo sapiens 151-155 21677353-8 2011 Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively. Metformin 9-18 solute carrier family 22 member 1 Homo sapiens 157-185 21677353-8 2011 Although metformin is not metabolized, the latest research has shown that it is actively transported into hepatocytes and renal tubular epithelium, by OCT1 (organic cation transporter 1, encoded by the SLC22A1 gene) and OCT2 (organic cation transporter 2, encoded by the SLC22A2 gene), respectively. Metformin 9-18 solute carrier family 22 member 1 Homo sapiens 202-209 20680652-1 2011 Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 64-71 20863201-6 2010 These results suggest that the inhibitory potential of sitagliptin on OCT1 may attenuate the first step of metformin action, that is, the phosphorylation of AMPK. Metformin 107-116 solute carrier family 22 member 1 Homo sapiens 70-74 20956498-0 2011 OCT1 Expression in adipocytes could contribute to increased metformin action in obese subjects. Metformin 60-69 solute carrier family 22 member 1 Homo sapiens 0-4 20956498-14 2011 Increased OCT1 gene expression in adipose tissue of obese subjects might contribute to increased metformin action in these subjects. Metformin 97-106 solute carrier family 22 member 1 Homo sapiens 10-14 21779389-1 2011 Metformin, an oral insulin-sensitizing drug, is actively transported into cells by organic cation transporters (OCT) 1, 2, and 3 (encoded by SLC22A1, SLC22A2, or SLC22A3), which are tissue specifically expressed at significant levels in various organs such as liver, muscle, and kidney. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 141-148 21779389-6 2011 All tested PPIs significantly inhibited metformin uptake by OCT1, OCT2, and OCT3 in a concentration-dependent manner. Metformin 40-49 solute carrier family 22 member 1 Homo sapiens 60-64 19591196-6 2009 Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells. Metformin 13-22 solute carrier family 22 member 1 Homo sapiens 44-48 20660041-0 2010 Organic cation transporter 1 polymorphisms predict the metabolic response to metformin in women with the polycystic ovary syndrome. Metformin 77-86 solute carrier family 22 member 1 Homo sapiens 0-28 20660041-2 2010 Organic cation transporter 1 (OCT1) plays a trigger role in the hepatic uptake of metformin. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 0-28 20660041-2 2010 Organic cation transporter 1 (OCT1) plays a trigger role in the hepatic uptake of metformin. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 30-34 20660041-3 2010 In cellular studies, it was recently shown that seven polymorphisms of OCT1 exhibit reduced transport of metformin. Metformin 105-114 solute carrier family 22 member 1 Homo sapiens 71-75 20660041-5 2010 OBJECTIVE: The aim was testing the hypothesis that polymorphisms in OCT1 may contribute to the variability in the response to metformin in PCOS. Metformin 126-135 solute carrier family 22 member 1 Homo sapiens 68-72 20660041-13 2010 CONCLUSIONS: Genetic variation in OCT1 may be associated with heterogeneity in the metabolic response to metformin in women with PCOS. Metformin 105-114 solute carrier family 22 member 1 Homo sapiens 34-38 20639304-1 2010 Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin. Metformin 135-144 solute carrier family 22 member 1 Homo sapiens 0-28 20639304-1 2010 Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin. Metformin 135-144 solute carrier family 22 member 1 Homo sapiens 30-34 20639304-1 2010 Organic cation transporter 1 (OCT1; SLC22A1) seems to play a role in the efficacy and disposition of the widely used antidiabetic drug metformin. Metformin 135-144 solute carrier family 22 member 1 Homo sapiens 36-43 20639304-4 2010 The goal of this study is to identify genetic variants of OCT1 in Chinese and Japanese populations, which may potentially modulate response to metformin. Metformin 143-152 solute carrier family 22 member 1 Homo sapiens 58-62 20639304-8 2010 The uptake of metformin in cells expressing Q97K, P117L, and R206C was significantly reduced relative to the OCT1 reference (62 +- 4.3, 55 +- 6.8, and 22 +- 1.5% for Q97K, P117L, and R206C, respectively). Metformin 14-23 solute carrier family 22 member 1 Homo sapiens 109-113 20639304-12 2010 This study suggests that nonsynonymous variants of OCT1 in Chinese and Japanese populations may affect the differential response to metformin. Metformin 132-141 solute carrier family 22 member 1 Homo sapiens 51-55 19898263-0 2010 Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response. Metformin 72-81 solute carrier family 22 member 1 Homo sapiens 41-45 19768675-1 2009 Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 135-163 19768675-1 2009 Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 165-170 20406215-10 2010 The hepatic uptake of metformin is mediated by organic cation transporters 1 and 3, and the liver is not important for the elimination or action of the dipeptidylpeptidase 4 inhibitors sitagliptin, vildagliptin and saxagliptin. Metformin 22-31 solute carrier family 22 member 1 Homo sapiens 47-82 19898263-1 2010 OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1). Metformin 11-20 solute carrier family 22 member 1 Homo sapiens 59-87 19898263-1 2010 OBJECTIVE: Metformin is transported into the hepatocyte by organic cation transporter 1 (OCT1) and out of the hepatocyte by multidrug and toxin extrusion 1 (MATE1). Metformin 11-20 solute carrier family 22 member 1 Homo sapiens 89-93 19898263-2 2010 Recently, we discovered that polymorphisms rs622342 A>C in the SLC22A1 gene, coding for OCT1, and rs2289669 G>A in the SLC47A1 gene, coding for MATE1, are associated with the degree of glucose lowering by metformin. Metformin 211-220 solute carrier family 22 member 1 Homo sapiens 66-73 19898263-2 2010 Recently, we discovered that polymorphisms rs622342 A>C in the SLC22A1 gene, coding for OCT1, and rs2289669 G>A in the SLC47A1 gene, coding for MATE1, are associated with the degree of glucose lowering by metformin. Metformin 211-220 solute carrier family 22 member 1 Homo sapiens 91-95 19898263-9 2010 CONCLUSION: The effect of the MATE1 rs2289669 polymorphism on the glucose lowering effect of metformin is larger in incident users with the OCT1 rs622342 CC genotype than in incident users with the AA genotype. Metformin 93-102 solute carrier family 22 member 1 Homo sapiens 140-144 19768675-0 2009 A comparison of uptake of metformin and phenformin mediated by hOCT1 in human hepatocytes. Metformin 26-35 solute carrier family 22 member 1 Homo sapiens 63-68 19381165-0 2009 Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Metformin 73-82 solute carrier family 22 member 1 Homo sapiens 25-53 19536068-0 2009 The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Metformin 119-128 solute carrier family 22 member 1 Homo sapiens 72-76 19536068-2 2009 We explored metformin pharmacokinetics in relation to genetic variations in OCT1, OCT2, OCT3, OCTN1, and MATE1 in 103 healthy male Caucasians. Metformin 12-21 solute carrier family 22 member 1 Homo sapiens 76-80 19536068-7 2009 Renal OCT1 expression may be important not only in relation to metformin but with respect to other drugs as well. Metformin 63-72 solute carrier family 22 member 1 Homo sapiens 6-10 19381165-1 2009 The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. Metformin 126-135 solute carrier family 22 member 1 Homo sapiens 4-32 19381165-1 2009 The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. Metformin 126-135 solute carrier family 22 member 1 Homo sapiens 49-56 19381165-2 2009 We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin. Metformin 110-119 solute carrier family 22 member 1 Homo sapiens 47-54 19381165-9 2009 To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus. Metformin 114-123 solute carrier family 22 member 1 Homo sapiens 50-57 19336679-0 2009 Reduced-function SLC22A1 polymorphisms encoding organic cation transporter 1 and glycemic response to metformin: a GoDARTS study. Metformin 102-111 solute carrier family 22 member 1 Homo sapiens 17-24 19336679-1 2009 OBJECTIVE: Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). Metformin 11-20 solute carrier family 22 member 1 Homo sapiens 95-100 19336679-1 2009 OBJECTIVE: Metformin is actively transported into the liver by the organic cation transporter (OCT)1 (encoded by SLC22A1). Metformin 11-20 solute carrier family 22 member 1 Homo sapiens 113-120 19336679-2 2009 In 12 normoglycemic individuals, reduced-function variants in SLC22A1 were shown to decrease the ability of metformin to reduce glucose excursion in response to oral glucose. Metformin 108-117 solute carrier family 22 member 1 Homo sapiens 62-69 19336679-3 2009 We assessed the effect of two common loss-of-function polymorphisms in SLC22A1 on metformin response in a large cohort of patients with type 2 diabetes. Metformin 82-91 solute carrier family 22 member 1 Homo sapiens 71-78 19336679-5 2009 R61C and 420del variants of SLC22A1 were genotyped in 3,450 patients with type 2 diabetes who were incident users of metformin. Metformin 117-126 solute carrier family 22 member 1 Homo sapiens 28-35 19002567-12 2009 CONCLUSION: The antidiabetic effect of metformin may be diminished in diabetic patients with EE cholestasis, due to impaired hepatic uptake of the drug via OCT1. Metformin 39-48 solute carrier family 22 member 1 Homo sapiens 156-160 19426682-7 2009 Metformin, which was also an anti-diabetic agent, and creatinine more potently inhibited the uptake of [(14)C]aminoguanidine by hOCT2 than that by hOCT1. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 147-152 18314419-6 2008 However, OATP-mediated BSP and pravastatin uptake and OCT1-mediated MPP(+) and metformin uptake were significantly inhibited by repaglinide (half-maximal inhibitory concentration [IC(50)] 1.6-5.6 micromol/l) and rosiglitazone (IC(50) 5.2-30.4 micromol/l). Metformin 79-88 solute carrier family 22 member 1 Homo sapiens 54-58 18788725-1 2008 The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. Metformin 134-143 solute carrier family 22 member 1 Homo sapiens 53-57 18788725-1 2008 The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. Metformin 134-143 solute carrier family 22 member 1 Homo sapiens 59-66 17609683-0 2008 Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Metformin 74-83 solute carrier family 22 member 1 Homo sapiens 35-63 18384255-6 2008 Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2. Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 99-103 17609683-0 2008 Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Metformin 74-83 solute carrier family 22 member 1 Homo sapiens 65-69 17609683-1 2008 The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin. Metformin 166-175 solute carrier family 22 member 1 Homo sapiens 80-108 17609683-1 2008 The goal of this study was to determine the effects of genetic variation in the organic cation transporter 1, OCT1, on the pharmacokinetics of the antidiabetic drug, metformin. Metformin 166-175 solute carrier family 22 member 1 Homo sapiens 110-114 17609683-4 2008 OCT1 genotypes had a significant (P<0.05) effect on metformin pharmacokinetics, with a higher area under the plasma concentration-time curve (AUC), higher maximal plasma concentration (Cmax), and lower oral volume of distribution (V/F) in the individuals carrying a reduced function OCT1 allele (R61C, G401S, 420del, or G465R). Metformin 55-64 solute carrier family 22 member 1 Homo sapiens 0-4 17609683-6 2008 Our studies suggest that OCT1 genotype is a determinant of metformin pharmacokinetics. Metformin 59-68 solute carrier family 22 member 1 Homo sapiens 25-29 17111267-0 2007 Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. Metformin 95-104 solute carrier family 22 member 1 Homo sapiens 34-38 17876861-3 2007 Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. Metformin 10-19 solute carrier family 22 member 1 Homo sapiens 58-63 17876861-3 2007 Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. Metformin 10-19 solute carrier family 22 member 1 Homo sapiens 150-155 17876861-3 2007 Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. Metformin 122-131 solute carrier family 22 member 1 Homo sapiens 58-63 17876861-3 2007 Uptake of metformin was facilitated by over-expression of hOCT1 and hOCT2 and showed saturable processes, indicating that metformin is a substrate of hOCT1 and hOCT2. Metformin 122-131 solute carrier family 22 member 1 Homo sapiens 150-155 17876861-4 2007 The IC(50) values of TAAs for hOCT2 were lower than hOCT1 and decreased with increasing alkyl chain length, indicating that the inhibitory potential of TAAs on metformin uptake was greater in hOCT2 than in hOCT1 and increased with increasing alkyl chain length. Metformin 160-169 solute carrier family 22 member 1 Homo sapiens 206-211 17600084-3 2007 Metformin has been shown to be transported by the human organic cation transporters 1 and 2 (hOCT1-2). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 56-91 17600084-3 2007 Metformin has been shown to be transported by the human organic cation transporters 1 and 2 (hOCT1-2). Metformin 0-9 solute carrier family 22 member 1 Homo sapiens 93-100 17476355-6 2007 make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422). Metformin 192-201 solute carrier family 22 member 1 Homo sapiens 106-134 17476355-6 2007 make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422). Metformin 192-201 solute carrier family 22 member 1 Homo sapiens 136-140 17111267-2 2007 In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin. Metformin 244-253 solute carrier family 22 member 1 Homo sapiens 38-42 17111267-5 2007 Age, body mass index (BMI) and treatment with lipid-lowering agents were demonstrated as positive predictors, and two mutations in the OCT1 gene, -43T > G in intron 1 and 408Met > Val (1222A > G) in exon 7, were negative and positive predictors, respectively, for the efficacy of metformin; the predictive accuracy was 55.5% (P < 0.05). Metformin 289-298 solute carrier family 22 member 1 Homo sapiens 135-139 16488580-8 2006 On the other hand, as in the case of metformin taken up by organic cation transporter 1, drug distribution to the tissue(s) may enhance its toxicity. Metformin 37-46 solute carrier family 22 member 1 Homo sapiens 59-87 16372821-15 2005 The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability. Metformin 14-23 solute carrier family 22 member 1 Homo sapiens 82-116