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The Effect of the Ala¹² Allele of the Peroxisome Proliferator-Activated Receptor-2 Gene on Skeletal Muscle Glucose Uptake Depends on Obesity: A Positron Emission Tomography Study

Department of Medicine (M.V., J.P., M.L.), University of Kuopio, 70211 Kuopio, Finland; and Positron Emission Tomography Center (P.N., K.H., K.A.V., R.L., P.P., J.K., A.P.M.V., J.K.), and Department of Medicine (P.N., T.T.), University of Turku, 20521 Turku, Finland

Address all correspondence and requests for reprints to: Dr. Markku Laakso, Department of Medicine, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. E-mail: markku.laakso{at}uku.fi.

Context: The Pro¹²Ala polymorphism of the peroxisome proliferator-activated receptor-2 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 subjects carrying the Ala¹² allele than in subjects carrying the Pro¹²Pro genotype (P = 0.004), whereas no differences were found in skeletal muscle perfusion between the groups. In contrast, in obese subjects the rates of skeletal muscle GU did not differ between carriers of the Ala¹² allele and carriers of the Pro¹²Pro genotype. No difference in adipose tissue GU was found in either nonobese or obese subjects according to Pro¹²Ala polymorphism.

Conclusions: We conclude that the Pro¹²Ala polymorphism modulates skeletal muscle GU differently in nonobese and obese subjects.

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