Abstract
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 language | English |
|---|---|
| Journal | Diabetes |
| Volume | 52 |
| Issue number | 3 |
| Pages (from-to) | 895-8 |
| Number of pages | 4 |
| ISSN | 0012-1797 |
| Publication status | Published - 2003 |
Keywords
- 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
