Stefan Norbert, Stumvoll Michael, Machicao Fausto, Koch Matthias, Häring Hans U, Fritsche Andreas
Department of Internal Medicine, Division of Endocrinology, Metabolism and Pathobiochemistry, University of Tübingen, Germany.
Obes Res. 2004 Apr;12(4):679-83. doi: 10.1038/oby.2004.78.
The common C825T polymorphism of the gene that encodes the G protein beta3 subunit has been shown to influence lipolysis in human adipocytes and to be associated with hypertension, body fat distribution, and obesity. In addition, it has been shown to be associated with insulin resistance in a small group of hypertensive subjects. We investigated whether this polymorphism contributed to the variability in obesity in our population from southern Germany and whether it was associated with insulin sensitivity of lipolysis and/or glucose disposal.
We determined percentage body fat, body fat distribution, glucose tolerance [oral glucose-tolerance test (OGTT)], insulin sensitivity, and serum free fatty acids using data from OGTTs (N = 774) and clamp (euglycemic hyperinsulinemic clamp, N = 216) in normal and impaired glucose tolerant subjects who were genotyped for this polymorphism.
Compared with noncarriers of the C825T mutation, subjects with the C825T variant (prevalence approximately 32%) had higher percentage body fat (p = 0.02) and higher BMI (p = 0.03). No conclusive effect was seen on serum free fatty acids measured either during fasting or at the end of a 2-hour OGTT. Insulin sensitivity determined during the OGTT and during the clamp, both adjusted for age, gender, and percentage body fat, was not different between the genotypes (p = 0.33 and p = 0.48, respectively).
We have concluded that the C825T polymorphism in the G protein beta3 subunit played an important role in the determination of obesity in this German population. However, it probably had no direct effects on insulin sensitivity of lipolysis and glucose disposal.
编码G蛋白β3亚基的基因常见的C825T多态性已被证明会影响人体脂肪细胞的脂解作用，并与高血压、体脂分布和肥胖相关。此外，在一小部分高血压患者中，该多态性还与胰岛素抵抗有关。我们研究了这种多态性是否导致了德国南部人群肥胖的差异，以及它是否与脂解作用的胰岛素敏感性和/或葡萄糖处置相关。
我们利用口服葡萄糖耐量试验（OGTT，N = 774）和钳夹试验（正常血糖高胰岛素钳夹试验，N = 216）的数据，在正常和糖耐量受损且已对该多态性进行基因分型的受试者中，测定了体脂百分比、体脂分布、葡萄糖耐量[口服葡萄糖耐量试验（OGTT）]、胰岛素敏感性和血清游离脂肪酸。
与C825T突变的非携带者相比，携带C825T变异体的受试者（患病率约为32%）体脂百分比更高（p = 0.02），BMI更高（p = 0.03）。在空腹或2小时OGTT结束时测量的血清游离脂肪酸方面，未观察到明确的影响。在调整了年龄、性别和体脂百分比后，OGTT期间和钳夹试验期间测定的胰岛素敏感性在不同基因型之间没有差异（分别为p = 0.33和p = 0.48）。
我们得出结论，G蛋白β3亚基中的C825T多态性在该德国人群肥胖的决定中起重要作用。然而，它可能对脂解作用的胰岛素敏感性和葡萄糖处置没有直接影响。
