A Gly482Ser missense mutation in the peroxisonte proliferator-activated receptor γ coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians
A Gly482Ser missense mutation in the peroxisonte proliferator-activated receptor γ coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians
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DOI：
10.2337/diabetes.52.3.895
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发表时间：
2003-03-01
期刊：
影响因子：
7.7
通讯作者：
Baier, L
中科院分区：
文献类型：
--
作者：
Muller, YL;Bogardus, C;Baier, L
过氧化物酶体增殖物激活受体γ共激活因子-1（Peroxisome Proliferator-activated Receptor gamma coactivator-1，PGC-1）是过氧化物酶体增殖物激活受体γ和α的转录共激活因子，在脂肪形成和脂质代谢中发挥重要作用。PGC-1基因编码区内的单核苷酸多态性预测了氨基酸482处的甘氨酸至丝氨酸的取代，并与丹麦人群中的2型糖尿病相关。在这项研究中，我们研究了这种Gly 482 Ser多态性是否与2型糖尿病或肥胖相关，或这些疾病的代谢预测因子，在皮马印第安人。Gly 482 Ser多态性与2型糖尿病或BMI无关（n = 984）。然而，在非糖尿病的皮马印第安人（n = 183-201），那些与Gly/Gly基因型有一个较低的平均胰岛素分泌反应静脉和口服葡萄糖和较低的平均速率的脂质氧化（超过24小时在呼吸室），尽管更大的平均皮下腹部脂肪细胞的大小和较高的平均血浆游离脂肪酸浓度。这些数据表明PGC-1中Gly 482 Ser错义多态性对脂质代谢具有代谢后果，其可能影响胰岛素分泌。
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 polymorphisin 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.