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 t...
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Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2003-03, Vol.52 (3), p.895 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0012-1797 |