scholarly journals Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study

Diabetes ◽  
2014 ◽  
Vol 64 (5) ◽  
pp. 1786-1793 ◽  
Author(s):  
Tanja Dujic ◽  
Kaixin Zhou ◽  
Louise A. Donnelly ◽  
Roger Tavendale ◽  
Colin N.A. Palmer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 1

scholarly journals Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes

2015 ◽  
Vol 33 (4) ◽  
pp. 511-514 ◽  
Author(s):  
T. Dujic ◽  
A. Causevic ◽  
T. Bego ◽  
M. Malenica ◽  
Z. Velija-Asimi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Gastrointestinal Side Effects ◽  
Organic Cation Transporter 1

scholarly journals Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes

Medicine ◽  
2018 ◽  
Vol 97 (27) ◽  
pp. e11349 ◽  
Author(s):  
Edith Pascale Mofo Mato ◽  
Magellan Guewo-Fokeng ◽  
M. Faadiel Essop ◽  
Peter Mark Oroma Owira
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Polymorphisms ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Metformin Therapy ◽  
Organic Cation Transporter 1

scholarly journals Variation in the plasma membrane monoamine transporter (PMAT, encoded in SLC29A4) and organic cation transporter 1 (OCT1, encoded in SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes: an IMI DIRECT study

2018 ◽  
Author(s):  
Adem Y Dawed ◽  
Kaixin Zhou ◽  
Nienke van Leeuwen ◽  
Anubha Mahajan ◽  
Neil Robertson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Plasma Membrane ◽  
Side Effects ◽  
Logistic Regression Model ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Gastrointestinal Intolerance ◽  
Gastrointestinal Side Effects ◽  
Organic Cation Transporter 1

AbstractObjectives20-30% of patients with metformin treated type 2 diabetes experience gastrointestinal side effects leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localised high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin into the circulation via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe GI side effects.Research Design and MethodsThe study included 286 severe metformin intolerant and 1128 tolerant individuals from the IMI DIRECT consortium. We assessed the association of patient characteristics, concomitant medication and the burden of mutations in the SLC29A4 and SLC22A1, genes that encode PMAT and OCT1, respectively, on odds of metformin intolerance using a logistic regression model.ResultsWomen (p < 0.001) and older people (p < 0.001) were more likely to develop metformin intolerance. Concomitant use of metformin transporter inhibiting drugs increased the odds of intolerance by more than 70% (OR = 1.72 [1.26-2.32], p < 0.001). In a logistic regression model adjusted for age, sex, weight and population substructure, the G allele at rs3889348 (SLC29A4) was associated with GI intolerance (OR = 1.34[1.09-1.65], p = 0.005). rs3889348 is the top cis-eQTL for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with metformin transporter inhibiting drugs had over three times higher odds of intolerance compared to carriers of no G allele and not treated with inhibiting drugs (OR = 3.23 [1.71-6.39], p < 0.001). Using a genetic risk score (GRS) derived from SLC29A4 (rs3889348) and previously reported SLC22A1 variants (M420del, R61C, G401S), the odds of intolerance was more than twice in individuals who carry three or more risk alleles compared with those carrying none (OR = 2.15 [1.20-4.12], p = 0.01).ConclusionsThese results suggest that intestinal metformin transporters and concomitant medications play an important role in gastrointestinal side effects of metformin.

The Polymorphic Variants rs3088442 and rs2292334 in the Organic Cation Transporter 3 (OCT3) Gene and Susceptibility Against Type 2 Diabetes: Role of their Interaction

2017 ◽  
Vol 48 (2) ◽  
pp. 162-168 ◽  
Author(s):  
Abdolkarim Mahrooz ◽  
Ahad Alizadeh ◽  
Mohammad Bagher Hashemi-Soteh ◽  
Maryam Ghaffari-Cherati ◽  
Seyyedeh Raheleh Hosseyni-Talei
Keyword(s):  
Type 2 Diabetes ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Polymorphic Variants ◽  
Organic Cation Transporter 3

scholarly journals Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-term response to metformin monotherapy in type 2 diabetes mellitus patients

2016 ◽  
Vol 175 (6) ◽  
pp. 531-540 ◽  
Author(s):  
Linda Zaharenko ◽  
Ineta Kalnina ◽  
Kristine Geldnere ◽  
Ilze Konrade ◽  
Solveiga Grinberga ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Nucleotide Polymorphisms ◽  
Pharmacokinetic Study ◽  
Organic Cation ◽  
Organic Cation Transporter ◽  
Nucleotide Polymorphisms ◽  
Short Term ◽  
Single Nucleotide ◽  
Flanking Region

Objective(s) High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-term efficiency. Design 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. Methods Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. Results In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 10−6 to 8.1 × 10−6). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. Conclusions For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5′ flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5′ flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.

L503F variant of carnitine/organic cation transporter 1 efficiently transports metformin and other biguanides

2016 ◽  
Vol 68 (9) ◽  
pp. 1160-1169 ◽  
Author(s):  
Azusa Futatsugi ◽  
Yusuke Masuo ◽  
Shiori Kawabata ◽  
Noritaka Nakamichi ◽  
Yukio Kato
Keyword(s):  
Organic Cation ◽  
Organic Cation Transporter ◽  
Organic Cation Transporter 1

scholarly journals The pregnane X receptor down-regulates organic cation transporter 1 (SLC22A1) in human hepatocytes by competing for (“squelching”) SRC-1 coactivator

2016 ◽  
Vol 173 (10) ◽  
pp. 1703-1715 ◽  
Author(s):  
Lucie Hyrsova ◽  
Tomas Smutny ◽  
Alejandro Carazo ◽  
Stefan Moravcik ◽  
Jana Mandikova ◽  
...  
Keyword(s):  
Organic Cation ◽  
Pregnane X Receptor ◽  
Organic Cation Transporter ◽  
Human Hepatocytes ◽  
Organic Cation Transporter 1
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