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

• Published in: The journal of clinical endocrinology and metabolism 2005-07, Vol.90 (7), p.4249-4254
• Main Authors: Vänttinen, Markku, Nuutila, Pirjo, Pihlajamäki, Jussi, Hällsten, Kirsti, Virtanen, Kirsi A., Lautamäki, Riikka, Peltoniemi, Pauliina, Kemppainen, Jukka, Takala, Teemu, Viljanen, Antti P. M., Knuuti, Juhani, Laakso, Markku
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Medical sciences; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2005-0101

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 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.