title: The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin.
abstract: OBJECTIVE
  Insulin resistance is characterized by impaired biological response of peripheral tissues to the metabolic effects of insulin. Organic cation transporter 2 (OCT2) is responsible for 80% metformin clearance. Limited information is available on the potential relationship between genetic variants of OCT2 and insulin resistance. In this study, we examined the role of OCT2-T201M (602 C>T) variant in insulin resistance in patients with type 2 diabetes (T2D) who were treated with metformin.
  
  
  METHODS
  Serum concentrations of insulin and C-peptide were assessed using ELISA. Homeostasis model assessment for insulin resistance (HOMA-IR) and HOMA for beta cell function (HOMA-BCF) were determined. PCR-based restriction fragment length polymorphism was used to genotype the OCT2-T201M variant.
  
  
  RESULTS
  Patients with minor alleles had higher HbA1c concentrations (p=0.019), fasting glucose levels (p=0.023), HOMA-IR (p=0.03), and HOMA-BCF (p=0.26) than patients with common alleles. Multivariate analysis identified a significant association between the variables OCT2-T201M and gender, with HOMA-IR and HOMA-BCF (Wilks' λ=0.549, F=12.71, p<0.001 for OCT2-T201M and Wilks' λ=0.369, F=26.46, p<0.001 for gender. Changes in HOMA-BCF were inversely correlated with changes in fasting glucose levels (r=-0.412, p=0.008) and HbA1c (r=-0.257, p=0.114).
  
  
  CONCLUSIONS
  Our findings suggest that the loss-of-function variant OCT2-T201M (rs145450955) contribute to changes in insulin resistance and beta cell activity in patients with T2D treated with metformin. Moreover, gender as an independent variable has a significant relationship with HOMA-BCF.
authors: Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Zahra
authors: Z
authors: Kashi
authors: Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Parisa
authors: P
authors: Masoumi
authors: Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: kmahrooz@yahoo.com.
authors: Abdolkarim
authors: A
authors: Mahrooz
authors: Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Mohammad Bagher
authors: MB
authors: Hashemi-Soteh
authors: Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
authors: Adele
authors: A
authors: Bahar
authors: Department of Epidemiology and Biostatistics, Faculty of Health, Tehran University of Medical Sciences, Tehran, Iran.
authors: Ahad
authors: A
authors: Alizadeh
mesh_terms: D002096:C-Peptide / Q000097:blood; D004247:DNA / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D011110:Polymorphism, Genetic
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D004247:DNA; D008687:Metformin
keywords: HOMA-BCF; HOMA-IR; Metformin; OCT2–T201M; Organic cation transporter; Type 2 diabetes