Article

Uncoupling protein 2 promoter polymorphism -866G/A affects its expression in beta-cells and modulates clinical profiles of Japanese type 2 diabetic patients.

First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
Diabetes (impact factor: 8.29). 03/2004; 53(2):482-5. pp.482-5
Source: PubMed

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.

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Keywords

adipose tissue
 
allele
 
allele frequency
 
Common uncoupling protein 2
 
ethnic difference
 
higher frequency
 
higher promoter activity
 
INS-1 beta-cell line
 
insulin secretion
 
insulin secretion capacity
 
Japanese population
 
Japanese study
 
Japanese type 2 diabetic patients
 
lean type 2 diabetic patients
 
modulates glucose-induced insulin secretion
 
morbid obesity
 
Type 2 diabetic patients
 
UCP2 expression
 
UCP2 promoter
 
UCP2 promoter polymorphism -866G/A
 

Miyoshi Sasahara