Single nucleotide polymorphisms in the peroxisome proliferator-activated receptor delta gene are associated with skeletal muscle glucose uptake.
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.
Vänttinen
Markku
M
Department of Medicine, University of Kuopio, 70210 Kuopio, Finland.
Nuutila
Pirjo
P
Kuulasmaa
Teemu
T
Pihlajamäki
Jussi
J
Hällsten
Kirsti
K
Virtanen
Kirsi A
KA
Lautamäki
Riikka
R
Peltoniemi
Pauliina
P
Takala
Teemu
T
Viljanen
Antti P M
AP
Knuuti
Juhani
J
Laakso
Markku
M
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
D007328:Insulin; D047494:PPAR delta; D005947:Glucose