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.
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.
Muller
Yunhua Li
YL
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease/NIH, 4212 N 16th Street, Phoenix, AZ 85016, USA.
Bogardus
Clifton
C
Pedersen
Oluf
O
Baier
Leslie
L
D017667:Adipocytes; D000273:Adipose Tissue; D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D015992:Body Mass Index; D048429:Cell Size; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005998:Glycine; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D015227:Lipid Peroxidation / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020125:Mutation, Missense; D009765:Obesity / Q000235:genetics; D017422:Sequence Analysis, DNA; D012694:Serine; D014157:Transcription Factors / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D012694:Serine; D005998:Glycine