Chiu K C, McCarthy J E
Division of Endocrinology and Metabolism, School of Medicine, University of California at Los Angeles 90095-1682, USA.
Biochem Biophys Res Commun. 1996 Apr 25;221(3):614-8. doi: 10.1006/bbrc.1996.0644.
We have previously reported a common variation in the liver promoter of the human glucokinase, which is regulated by insulin, in the patients with non-insulin-dependent diabetes mellitus (NIDDM). The variation occurred within a 10-bp region completely conserved between human and rat. Its basic motif was almost identical to the insulin regulatory element of the phosphoenolpyruvate carboxykinase gene. In vitro transfection experiment showed that the G-to-A variation causes a 58% reduction in the promoter activity. After oral glucose challenge, the homozygous A/A subjects had the highest stimulated insulin levels at 60 and 90 minutes and the highest insulin area under the curve as compared to the subjects with other genotypes, which suggested the homozygous A/A subjects were more insulin resistant. As insulin resistance is a risk factor of NIDDM, we concluded that this promoter variation is a risk factor for NIDDM.
我们之前报道过，在非胰岛素依赖型糖尿病（NIDDM）患者中，人类葡萄糖激酶肝脏启动子存在一种常见变异，该启动子受胰岛素调节。这种变异发生在人与大鼠之间完全保守的一个10bp区域内。其基本基序与磷酸烯醇式丙酮酸羧激酶基因的胰岛素调节元件几乎相同。体外转染实验表明，G到A的变异导致启动子活性降低58%。口服葡萄糖激发试验后，与其他基因型的受试者相比，纯合子A/A受试者在60分钟和90分钟时的刺激胰岛素水平最高，曲线下胰岛素面积最大，这表明纯合子A/A受试者胰岛素抵抗更强。由于胰岛素抵抗是NIDDM的一个危险因素，我们得出结论，这种启动子变异是NIDDM的一个危险因素。
