Jacob S, Stumvoll M, Becker R, Koch M, Nielsen M, Löblein K, Maerker E, Volk A, Renn W, Balletshofer B, Machicao F, Rett K, Häring H U
Dept. of Endocrinology, University of Tübingen, Germany.
Horm Metab Res. 2000 Oct;32(10):413-6. doi: 10.1055/s-2007-978663.
Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.
最近，有人描述了PPARγ2受体的一种高度常见的多态性（Pro12Ala），并发现其与转录活性降低有关。人和动物研究均表明，这种多态性可能与胰岛素敏感性增加有关。然而，尚未证明其存在独立于其他已知影响胰岛素敏感性因素的效应。因此，我们采用高胰岛素正葡萄糖钳夹技术，对37名携带PPARγ2-Pro12Ala突变的杂合子受试者和37名PPARγ2-Pro12Ala阴性的对照受试者的胰岛素敏感性进行了比较。对照组是从190名受试者中通过按性别、体重指数、脂肪分布和身体组成进行配对选取的。在多态性杂合子组中，钳夹期间的稳态血浆胰岛素水平（63.3微单位/毫升±2.8）显著低于对照组（74.9微单位/毫升±4.0，p = 0.02）。虽然PPARγ2-Pro12Ala组（8.1毫升/千克×分钟×100±0.5）和对照组（7.6毫升/千克×分钟×100±3.0，p = 0.7）的葡萄糖代谢清除率相似，但PPARγ2-Pro12Ala组的胰岛素敏感性指数显著更高（12.5毫克/千克×分钟×微单位/毫升±0.9对9.7毫克/千克×分钟×微单位/毫升±0.8，p = 0.039）。此外，还发现PPARγ2-Pro12Ala组的任意脂解指数（游离脂肪酸降低值除以胰岛素增加值）略高于对照组（8.0±0.9对6.1±0.7，p = 0.097）。总之，这些数据表明，PPARγ2-Pro12Ala突变与更好的葡萄糖处置胰岛素敏感性相关，可能还与抗脂解作用有关。
