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

被引:19
作者
Vänttinen, M
Nuutila, P
Pihlajamäki, J
Hällsten, K
Virtanen, KA
Lautamäki, R
Peltoniemi, P
Kemppainen, J
Takala, T
Viljanen, APM
Knuuti, J
Laakso, M [1 ]
机构
[1] Univ Kuopio, Dept Med, Kuopio 70211, Finland
[2] Univ Turku, Positron Emiss Tomog Ctr, Turku 20521, Finland
[3] Univ Turku, Dept Med, Turku 20521, Finland
关键词
D O I
10.1210/jc.2005-0101
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: The Pro(12)Ala polymorphism of the peroxisome proliferator-activated receptor-gamma 2 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. 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/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, [O-15] H2O, 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.
引用
收藏
页码:4249 / 4254
页数:6
相关论文
共 47 条
[31]   GRAPHICAL EVALUATION OF BLOOD-TO-BRAIN TRANSFER CONSTANTS FROM MULTIPLE-TIME UPTAKE DATA - GENERALIZATIONS [J].
PATLAK, CS ;
BLASBERG, RG .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1985, 5 (04) :584-590
[32]   Lumped constant for [18F] fluorodeoxyglucose in skeletal muscles of obese and nonobese humans [J].
Peltoniemi, P ;
Lönnroth, P ;
Laine, H ;
Oikonen, V ;
Tolvanen, T ;
Grönroos, T ;
Strindberg, L ;
Knuuti, J ;
Nuutila, P .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2000, 279 (05) :E1122-E1130
[33]   The Pro12Ala polymorphism of the PPARγ2 gene regulates weight from birth to adulthood [J].
Pihlajamäki, J ;
Vanhala, M ;
Vanhala, P ;
Laakso, M .
OBESITY RESEARCH, 2004, 12 (02) :187-190
[34]   Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake [J].
Pitkänen, OP ;
Laine, H ;
Kemppainen, J ;
Eronen, E ;
Alanen, A ;
Raitakari, M ;
Kirvelä, O ;
Ruotsalainen, U ;
Knuuti, J ;
Koivisto, VA ;
Nuutila, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1999, 521 (03) :729-737
[35]   The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome:: results from the Quebec Family Study [J].
Robitaille, J ;
Després, JP ;
Pérusse, L ;
Vohl, MC .
CLINICAL GENETICS, 2003, 63 (02) :109-116
[36]  
Ruotsalainen U, 1997, J NUCL MED, V38, P314
[37]  
Sipila H. T., 2001, Journal of Labelled Compounds and Radiopharmaceuticals, V44, pS1066
[38]   [DEOXYGLUCOSE-C-14 METHOD FOR MEASUREMENT OF LOCAL CEREBRAL GLUCOSE-UTILIZATION - THEORY, PROCEDURE, AND NORMAL VALUES IN CONSCIOUS AND ANESTHETIZED ALBINO-RAT [J].
SOKOLOFF, L ;
REIVICH, M ;
KENNEDY, C ;
DESROSIERS, MH ;
PATLAK, CS ;
PETTIGREW, KD ;
SAKURADA, O ;
SHINOHARA, M .
JOURNAL OF NEUROCHEMISTRY, 1977, 28 (05) :897-916
[39]   The peroxisome proliferator-activated receptor-γ2 pro12Ala polymorphism [J].
Stumvoll, M ;
Häring, H .
DIABETES, 2002, 51 (08) :2341-2347
[40]   Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with increased antilipolytic insulin sensitivity [J].
Stumvoll, M ;
Wahl, HG ;
Löblein, K ;
Becker, R ;
Machicao, F ;
Jacob, S ;
Häring, H .
DIABETES, 2001, 50 (04) :876-881