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

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 12; pp. 3587 - 3591
• Main 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, Laakso, Markku
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-12-2005
• Subjects: Adipose Tissue - metabolism; Adult; Biological and medical sciences; Biological Transport - genetics; Care and treatment; Chromosome Mapping; Diabetes; Diabetes mellitus; Diabetes. Impaired glucose tolerance; Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Health aspects; Humans; Insulin - physiology; Male; Medical sciences; Muscle, Skeletal - metabolism; Polymorphism, Single Nucleotide; PPAR delta - genetics; Risk factors; Single nucleotide polymorphisms; Striated muscle. Tendons; Vertebrates: osteoarticular system, musculoskeletal system; United Kingdom; Endocrinopathy; Gene; Diabetes mellitus; Glucose; Striated muscle; Uptake; Peroxisome proliferator activated receptor; Polymorphism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.12.3587

Single Nucleotide Polymorphisms in the Peroxisome Proliferator–Activated Receptor δ Gene Are Associated With Skeletal Muscle
Glucose Uptake
Markku Vänttinen 1 ,
Pirjo Nuutila 2 3 ,
Teemu Kuulasmaa 1 ,
Jussi Pihlajamäki 1 ,
Kirsti Hällsten 2 ,
Kirsi A. Virtanen 2 ,
Riikka Lautamäki 2 ,
Pauliina Peltoniemi 2 ,
Teemu Takala 2 3 ,
Antti P.M. Viljanen 2 ,
Juhani Knuuti 2 and
Markku Laakso 1
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
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
Abstract
The peroxisome proliferator–activated receptors (PPARs) belong to a superfamily of nuclear receptors. It includes PPAR-δ,
a key regulator of fatty acid oxidation and energy uncoupling, universally expressed in different tissues. The PPAR-δ 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 ([ 18 F]FDG) and positron emission tomography (PET). Three of six SNPs of PPARD and their haplogenotypes were significantly associated
with whole-body insulin sensitivity. [ 18 F]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.
[18F]FDG, fluorine-18–labeled fluorodeoxyglucose
PET, positron emission tomography
PPAR, peroxisome proliferator–activated receptor
PPARD, PPAR-δ gene
SNP, single nucleotide polymorphism
WBGU, whole-body glucose uptake
Footnotes
M.V. and P.N. contributed equally to this article.
Accepted September 19, 2005.
Received August 5, 2005.
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