Microsatellite And Single Nucleotide Polymorphisms In The Insulin Like Growth Factor 1 Promoter With Insulin Sensitivity

Insulin like growth factor 1(IGF1)is a peptide hormone and it plays important roles in the process of cell growth,proliferation and apoptosis.Meanwhile,IGF1 also has insulin-like metabolic effect,playing important roles in regulating glucose homeostasis and insulin sensitivity.Insulin resistance is the reduction of insulin promoting glucose uptake function and the compensatory over-secretion of insulin and the subsequent hyperinsulinemia.In recent years,many studies have shown that IGF1 plays an important role in insulin resistance.However,investigations of CA microsatellite and single nucleotide polymorphisms(SNPs)in the evolutionarily conserved region(ECR)of IGF1 promoter with insulin sensitivity came to inconsistent conclusions.Objective: The aim of this study was to investigate associations of the CA microsatellite and rs35767,rs5742612,rs2288377 polymorphisms and the SNP haplotypes with and without CA microsatellite in the IGF1 promoter with insulin sensitivity and secretion.Methods: This study included 389 type 2 diabetes mellitus patients.Venous blood was collected after 8 hours fasting for the test of glucose,insulin,peptide C,IGF1,Hb A1 c and serum lipid parameters.All participants underwent a 75 g oral glucose tolerance test(OGTT),with 60-min and 120-min venous blood collected for the test of glucose,insulin and peptide C.The CA microsatellite and SNPs were genotyped in389 type 2 diabetes mellitus(T2DM)patients.Associations of the genotypes and haplotypes with insulin sensitivity,insulin secretion,glucose tolerance and IGF1 were analyzed by ANCOVA(general linear model)and multiple linear regression.Results: The C allele of rs5742612 was found to be associated with decreased indicates of insulin sensitivity(HOMA-S index,?=-0.131,P=0.008;fasting insulin level,?=0.022,P=0.006)and increased insulin secretion(HOMA-B index,?=0.099,P=0.008;insulin AUC,?=0.112,P=0.012)after controlling for the effects of gender,age and BMI according to the multiple linear regression model.The linear regression model also indicated that the A allele of rs2288377 was associated with decreased insulin sensitivity(HOMA-S index,?=-0.159,P=0.001;fasting insulin,?=0.143,P=0.001)and increased insulin secretion(HOMA-B index,?=0.114,P=0.017;insulin AUC,?=0.042,P=0.002),independent of gender,age and BMI.The SNP haplotype showed significant association with circulating IGF1 levels,?=0.026,P=0.042,after adjusting gender,age and BMI.The CA microsatellite,rs35767 polymorphisms and SNP haplotype with or without CA showed no significant association with metabolic parameters.rs5742612 and rs2288377 polymorphisms showed no correlation with IGF1 levels.Conclusions: The rs5742612 and rs2288377 polymorphisms are significantly associated with insulin biology with TT genotype exhibiting higher insulin sensitivity and lower insulin secretion,as compared with carriers of the C allele and A allele,respectively.The CA microsatellite,rs35767,SNP haplotype and SNPs haplotype have no genotype-related difference of insulin sensitivity or secretion.