Results
Title

Single nucleotide polymorphisms in the peroxisome proliferator-activated receptor delta gene are associated with skeletal muscle glucose uptake.

Authors

Vänttinen, Markku; Nuutila, Pirjo; Kuulasmaa, Teemu; Pihlajamäki, Jussi; Hällsten, Kirsti; Virtanen, Kirsi A.; Lautamäki, Riikka; Peltoniemi, Pauliina; Takala, Teemu; Viljanen, Antti P. M.; Knuuti, Juhani; Laaksos, Markku; Vänttinen, Markku; Pihlajamäki, Jussi; Hällsten, Kirsti; Lautamäki, Riikka; Laakso, Markku

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.

Subjects

PEROXISOMES; NUCLEAR receptors (Biochemistry); NUCLEOTIDES; GENETIC polymorphisms; ADIPOSE tissues; GLUCOSE; POSITRON emission tomography; GLUCOSE metabolism; BIOLOGICAL transport; COMPARATIVE studies; GENE mapping; INSULIN; RESEARCH methodology; MEDICAL cooperation; PROTEINS; RESEARCH; EVALUATION research; SKELETAL muscle

Publication

Diabetes, 2005, Vol 54, Issue 12, p3587

ISSN

0012-1797

Publication type

Academic Journal

DOI

10.2337/diabetes.54.12.3587