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Diabetes Res Clin Pract. 2015 Apr;108(1):78-83. doi: 10.1016/j.diabres.2015.01.024. Epub 2015 Jan 21.

The variant organic cation transporter 2 (OCT2)-T201M contribute to changes in insulin resistance in patients with type 2 diabetes treated with metformin.

Author information

1
Diabetes Research Center, Imam Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
2
Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
3
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.
4
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.
5
Department of Epidemiology and Biostatistics, Faculty of Health, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

AIMS:

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.

KEYWORDS:

HOMA-BCF; HOMA-IR; Metformin; OCT2–T201M; Organic cation transporter; Type 2 diabetes

PMID:
25662675
DOI:
10.1016/j.diabres.2015.01.024
[Indexed for MEDLINE]

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