A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians

Research output: Contribution to journalJournal articleResearchpeer-review

Yunhua Li Muller, Clifton Bogardus, Oluf Pedersen, Leslie Baier

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) is a transcriptional coactivator of peroxisome proliferator-activated receptor gamma and alpha, which play important roles in adipogenesis and lipid metabolism. A single nucleotide polymorphism within the coding region of the PGC-1 gene predicts a glycine to serine substitution at amino acid 482 and has been associated with type 2 diabetes in a Danish population. In this study, we examined whether this Gly482Ser polymorphism is associated with type 2 diabetes or obesity, or metabolic predictors of these diseases, in Pima Indians. There was no association of the Gly482Ser polymorphism with either type 2 diabetes or BMI (n = 984). However, among nondiabetic Pima Indians (n = 183-201), those with the Gly/Gly genotype had a lower mean insulin secretory response to intravenous and oral glucose and a lower mean rate of lipid oxidation (over 24 h in a respiratory chamber) despite a larger mean subcutaneous abdominal adipocyte size and a higher mean plasma free fatty acid concentration. These data indicate that the Gly482Ser missense polymorphism in PGC-1 has metabolic consequences on lipid metabolism that could influence insulin secretion.
Original languageEnglish
JournalDiabetes
Volume52
Issue number3
Pages (from-to)895-8
Number of pages4
ISSN0012-1797
Publication statusPublished - 2003

    Research areas

  • Adipocytes, Adipose Tissue, Adult, Alleles, Blood Glucose, Body Composition, Body Mass Index, Cell Size, Diabetes Mellitus, Type 2, Female, Gene Frequency, Glycine, Humans, Indians, North American, Insulin, Lipid Peroxidation, Longitudinal Studies, Male, Mutation, Missense, Obesity, Sequence Analysis, DNA, Serine, Transcription Factors

ID: 38454540