0eb288ed-031a-4223-bd62-bcfb75d6df76
title
Uncoupling protein 2  promoter polymorphism  -866G/A  affects its expression in beta-cells and modulates clinical profiles of Japanese type 2 diabetic patients.
921ebc61-d950-4c08-bb5e-7d0abaa01a79
abstract
Common uncoupling protein 2 ( UCP2 ) promoter polymorphism  -866G/A  is reported to be associated with its expression in adipose tissue and the risk of obesity in Caucasians. On the other hand, several studies suggested that  UCP2  expression in beta-cells is an important determinant of  insulin  secretion. In the Japanese population, morbid obesity is very rare, and  insulin  secretion capacity is relatively low as compared with Caucasians. Because  UCP2  would link to  insulin  secretion and obesity, it might explain this ethnic difference. Here, we report that the  UCP2  promoter with the A allele showed higher promoter activity in the INS-1 beta-cell line. The frequency of the A allele is higher in our Japanese study than that in Caucasians. Type 2 diabetic patients with the A allele need  insulin  therapy earlier and showed higher frequency of  insulin  treatment. Moreover glucose-induced early  insulin  secretion is significantly lower in patients with the A allele. However, there was no difference in allele frequency between obese and lean type 2 diabetic patients. In conclusion,  UCP2  promoter polymorphism  -866G/A  does not affect obesity in Japanese type 2 diabetic patients but affects its transcription in beta-cells and modulates glucose-induced  insulin  secretion and eventually  insulin  requirement in Japanese type 2 diabetic patients. Higher A allele frequency in the Japanese population might partly explain the ethnic difference of  insulin  secretion capacity.