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Diabetes 54:3587-3591, 2005
© 2005 by the American Diabetes Association, Inc.

Brief Genetics Reports

Single Nucleotide Polymorphisms in the Peroxisome Proliferator–Activated Receptor {delta} Gene Are Associated With Skeletal Muscle Glucose Uptake

Markku Vänttinen1, Pirjo Nuutila2,3, Teemu Kuulasmaa1, Jussi Pihlajamäki1, Kirsti Hällsten2, Kirsi A. Virtanen2, Riikka Lautamäki2, Pauliina Peltoniemi2, Teemu Takala2,3, Antti P.M. Viljanen2, Juhani Knuuti2, and Markku Laakso1

1 Department of Medicine, University of Kuopio, Kuopio, Finland
2 Positron Emission Tomography Centre, University of Turku, Turku, Finland
3 Department of Medicine, University of Turku, Turku, Finland

The peroxisome proliferator–activated receptors (PPARs) belong to a superfamily of nuclear receptors. It includes PPAR-{delta}, a key regulator of fatty acid oxidation and energy uncoupling, universally expressed in different tissues. The PPAR-{delta} gene (PPARD) maps to 6p21.2-p21.1 and has 11 exons and spans 35 kbp. We investigated the effects of single nucleotide polymorphisms (SNPs) of PPARD on whole-body, skeletal muscle, and subcutaneous adipose tissue glucose uptake in 129 healthy individuals using the hyperinsulinemic-euglycemic clamp technique combined with fluorine-18–labeled fluorodeoxyglucose ([18F]FDG) and positron emission tomography (PET). Three of six SNPs of PPARD and their haplogenotypes were significantly associated with whole-body insulin sensitivity. [18F]FDG-PET scanning indicated that SNPs of PPARD primarily affected insulin sensitivity by modifying glucose uptake in skeletal muscle but not in adipose tissue. Our results give evidence that SNPs of PPARD regulate insulin sensitivity particularly in skeletal muscle.

Address correspondence and reprint requests to Markku Laakso, MD, Academy Professor, Department of Medicine, University of Kuopio, 70210 Kuopio, Finland. E-mail: markku.laakso{at}kuh.fi

Abbreviations: [18F]FDG, fluorine-18–labeled fluorodeoxyglucose; PET, positron emission tomography; PPAR, peroxisome proliferator–activated receptor; PPARD, PPAR-{delta} gene; SNP, single nucleotide polymorphism; WBGU, whole-body glucose uptake


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