title: Single nucleotide polymorphisms in the peroxisome proliferator-activated receptor delta gene are associated with skeletal muscle glucose uptake.
abstract: 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.
authors.affiliation: Department of Medicine, University of Kuopio, 70210 Kuopio, Finland.
authors.forename: Markku
authors.initials: M
authors.lastname: Vänttinen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Teemu
authors.initials: T
authors.lastname: Kuulasmaa
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Kirsti
authors.initials: K
authors.lastname: Hällsten
authors.forename: Kirsi A
authors.initials: KA
authors.lastname: Virtanen
authors.forename: Riikka
authors.initials: R
authors.lastname: Lautamäki
authors.forename: Pauliina
authors.initials: P
authors.lastname: Peltoniemi
authors.forename: Teemu
authors.initials: T
authors.lastname: Takala
authors.forename: Antti P M
authors.initials: AP
authors.lastname: Viljanen
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001692:Biological Transport / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D047494:PPAR delta / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D007328:Insulin; D047494:PPAR delta; D005947:Glucose