The effect of the Ala12 allele of the peroxisome proliferator-activated receptor-gamma2 gene on skeletal muscle glucose uptake depends on obesity: a positron emission tomography study.
BACKGROUND
The Pro(12)Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene is associated with insulin sensitivity. Obesity is a major risk factor for insulin resistance, but the association of the Pro(12)Ala 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 Pro(12)Ala polymorphism on skeletal muscle and adipose tissue glucose uptake (GU) in nonobese and obese subjects.


METHODS
The design was a cross-sectional study.


METHODS
The rates of GU were investigated in 124 (72 nonobese and 52 obese; body mass index cutoff point, 27 kg/m(2)) healthy subjects with the euglycemic hyperinsulinemic clamp. Skeletal muscle and adipose tissue GU and skeletal muscle perfusion were measured using fluorine-18-labeled fluorodeoxyglucose, [(15)O]H(2)O, and positron emission tomography.


RESULTS
The rates of skeletal muscle GU were higher in nonobese subjects carrying the Ala(12) allele than in subjects carrying the Pro(12)Pro 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 Ala(12) allele and carriers of the Pro(12)Pro genotype. No difference in adipose tissue GU was found in either nonobese or obese subjects according to Pro(12)Ala polymorphism.


CONCLUSIONS
We conclude that the Pro(12)Ala polymorphism modulates skeletal muscle GU differently in nonobese and obese subjects.
Vänttinen
Markku
M
Department of Medicine, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. markku.laakso@uku.fi
Nuutila
Pirjo
P
Pihlajamäki
Jussi
J
Hällsten
Kirsti
K
Virtanen
Kirsi A
KA
Lautamäki
Riikka
R
Peltoniemi
Pauliina
P
Kemppainen
Jukka
J
Takala
Teemu
T
Viljanen
Antti P M
AP
Knuuti
Juhani
J
Laakso
Markku
M
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000483:Alleles; D003430:Cross-Sectional Studies; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography
D005230:Fatty Acids, Nonesterified; D047495:PPAR gamma; D005947:Glucose