The Effect of the Ala12 Allele of the Peroxisome Proliferator-Activated Receptor-γ2 Gene on Skeletal Muscle Glucose Uptake Depends on Obesity: A Positron Emission Tomography Study

Context: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene is associated with insulin sensitivity. Obesity is a major risk factor for insulin resistance, but the association of the Pro12Ala polymorphism with body weight has been controversial. Furthermore, obesity may modulate the effect of this polymorphism on insulin sensitivity. Objective: The aim of our study was to investigate the effects of the Pro12Ala polymorphism on skeletal muscle and adipose tissue glucose uptake (GU) in nonobese and obese subjects. Design: The design was a cross-sectional study. Study Subjects: The rates of GU were investigated in 124 (72 nonobese and 52 obese; body mass index cutoff point, 27 kg/m2) healthy subjects with the euglycemic hyperinsulinemic clamp. Skeletal muscle and adipose tissue GU and skeletal muscle perfusion were measured using fluorine-18-labeled fluorodeoxyglucose, [15O]H2O, and positron emission tomography. Results: The rates of skeletal muscle GU were higher in nonobese ...