The influence of the Pro12Ala mutation of PPARγ2 receptor gene on β-cells restoration and insulin resistance in type 2 diabetes with hypertension

Abstract

The aim of this investigation was to determine whether a PPARγ2 Pro12Ala polymorphism was associated with insulin resistance, β-cell function and hypertension in Chinese populations. 289 unrelated Chinese subjects first diagnosed Type 2 diabetes (HbAC1<6.0) were investigated, including 132 hypertensive diabetic (HTD) subjects, 157 normotensive diabetic (NTD) subjects. Blood pressure and anthropometric measurements were collected from all participants, as well as several venous blood samples during oral glucose tolerance test (OGTT). Biochemical measurements (high-density lipoprotein (HDL) and low-density lipoprotein-cholesterol (LDL), triglycerides) and PPARγ2 Pro12Ala genotype were also determined. And insulin resistance and β-cells function was assessed by HOMA-IR and HOMA-β respectively. The frequency of subjects bearing the Pro12Ala was lower in the hypertension group (3.03%) than in the non-hypertension group (5.7%) (P<0.05) after adjusted for age, BMI and gender. Hypertensive diabetic Pro12Ala subjects had lower fasting plasma glucose level (P=0.0127), and better glucose tolerance 60 min after oral glucose (P=0.0361). Moreover, plasma insulin concentrations at 60 min was lower than those without A variant (P=0.0275), and both hypertensive Ala/Pro in HOMA-β (P=0.0455) and AUC for insulin (P=0.0473) were higher, and HOMA-IR was lower (P=0.0375) as compared with hypertensive Pro/Pro subjects. No association was observed between Pro12Ala genotype and BMI, total cholesterol, HDL- cholesterol or triglycerides in either group. Our findings suggested that the Ala 12 allele of the PPARγ2 gene may improve insulin resistance and ameliorate β-cell function reserves in T2DM with hypertension, and protect patients from hypertension in T2DM. As an important thrifty gene, environment factors may exerts an effect of PPAR γ2 on glucose homeostasis and insulin resistance.

Keywords

peroxisome proliferator-activated receptor γ2 / polymorphism / hypertension / insulin resistance / β-cell function

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