| Aims:Insulin-secreting depends on the closure of ATP-sensitive potassium(KATP) channel in isletβ-cell membrane,Sulfonylurea receptor 1(SUR1) and the uncoupling protein 2(UCP2) have had a significant impact on insulin secretion through affecting KATP channel,and mediated the hypoglycemic effect of repaglinide,an non-sulfonylurea insulin secretagogue.The present study aimed at investigating the association between SUR1 gene 16 exon -3c/t,UCP2 gene -866G/A polymorphisms and the pathogenesis of type 2 diabetes mellitus(T2DM) as well as their effects on repaglinide response in patients with T2DM.Methods:370 patients with T2DM(185 males and 185 females) and 166 healthy volunteers(95 males and 71 females) in Hunan were included.Genomic DNA was extracted from white cells of peripheral blood,Genotyping were determined using the PCR-RFLP and identified by sequencing.According to different genotypes,60 patients(20 patients of each genotype) with T2DM were selected to orally administered with 1mg repaglinide three times a day for 12 consecutive weeks.Plasma concentration of glycated hemoglobin(HbAlc),serum fasting blood glucose(FBG) and serum fasting insulin(FINS),postprandial blood glucose(PBG30,PBG60,PBG120) and postprandial insulin(PINS30, PINS60,PINS120) after bread meal(100 grams) 30,60 and 120 minutes were determined at 0 and 12th weekend after administration,homeostasis model assessment for insulin resistance(HOMA-IR),homeostasis model assessment for beta cell function(HOMA-β) and early insulin secretion index(ΔI30/ΔG30) were calculated.Statistical analyses were performed by one-way ANOVA,paired t-test and Chi-square(x2).Results:(1)The two polymorphisms of SUR1 and UCP2 genes were in Hardy-Weinberg equilibrium.(2)The allelic frequency of 16-3t(SUR1) in patients with T2DM and health control were 57.2%and 48.2%, respectively.Significant difference was observed between two groups (P＜0.01).Further study showed that there were significant differences in the levels of HbAlc,PINS30,PINS60 andΔI30/ΔG30 among different genotypes of SUR1 gene in T2DM patients(P＜0.05),Patients with tt genotype of SUR1(16-3c/t) had bigger HbAlc than that in cc and ct genotypes and smaller PINS30,PINS60 than that in cc genotypes,patients with cc genotypes had biggerΔI30/ΔG30 than that in ct and tt genotypes (P＜0.05);No significant difference was observed among three groups after 12 weeks of repaglinide treatment(P＞0.05).(3)The allelic frequency of-866A(UCP2) in patients with T2DM and health control were 46.6% and 45.5%,respectively,No significant difference was observed between two groups(P＞0.05).But there were significant differences in the levels of FBG,PBG30,PBG60,PBG120,HbAlc,PINS30,PINS60,PINS120, HOMA-βandΔI30/ΔG30 among different genotypes of UCP2 gene in T2DM patients(P＜0.05),Patients with AA genotype of UCP2(-866G/A) had bigger FBG,PBG30,PBG60,PBG120,HbAlc and smaller PINS30, PINS60,PINS120,HOMA-β,ΔI30/ΔG30 than that in GG genotypes. and patients with GG genotype of UCP2(-866G/A) had higher differential values(after and before administration) in PINS30 and HbAlc than that in AA genotype after 12 weeks of repaglinide treatment (P＜0.05)Conclusions:(1) There is significant difference in allelic frequency of SUR1 gene 16-3c/t between T2DM group and health control group,the genetic polymorphisms appear to be influence on the development of T2DM and insulin secretion of isletβ-cell,but not on the therapeutic efficacy of repaglinide.(2) There is no difference in allelic frequency of UCP2 gene -866G/A between T2DM group and health control group,But the genetic polymorphism of UCP2 gene-866G/A could contribute to the defect of insulin secretion in T2DM and might affect the role of increasing PINS30 and lowering HbAlc of repaglinide in patients with T2DM. |
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