Insulin sensitivity is not affected by mutation of codon 972 of the human IRS-I gene
Insulin sensitivity is not affected by mutation of codon 972 of the human IRS-I gene
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DOI：
10.1159/000023466
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发表时间：
1999-11-01
期刊：
影响因子：
--
通讯作者：
Sumida, Y
中科院分区：
文献类型：
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作者：
Ito, K;Katsuki, A;Sumida, Y
我们研究了胰岛素受体底物-1 （IRS-1）基因密码子972多态性与日本人群胰岛素抵抗的关系。在130例2型糖尿病（DM）患者中，我们发现6例Gly972Arg突变为杂合。在744名健康受试者中，6名为杂合子，1名为纯合子。对6例Gly972Arg杂合突变的糖尿病患者中的3例和60例无杂合突变的糖尿病患者进行了高胰岛素正糖钳夹研究。两组胰岛素敏感性水平基本相同（葡萄糖输注率，GIR = 50.2 +/- 3.0 vs. 51.3 +/- 12.1 mu mol/kg/min）。同样，使用稳态模型评估，有和没有突变的健康受试者之间的胰岛素敏感性没有差异（HOMA指数= 1.14 +/- 0.50 vs 1.02 +/- 0.63）。糖尿病患者中Gly972Arg等位基因的频率与对照组相比没有增加，即使是在年龄（50 ~ 50岁）或肥胖（BMI大于等于25）的受试者中。在健康受试者中，我们发现了一名25岁的男性携带纯合子Gly972Arg等位基因。轻度肥胖（BMI = 25.5），但胰岛素敏感性较高，与未发生突变的健康受试者相当（GIR = 67.2 vs. 71.8 +/- 22.0 mu mol/kg/min）。由于健康受试者的GIR明显高于2型糖尿病患者，我们推测糖尿病患者中可能存在另一种对胰岛素敏感性产生更有害影响的遗传或环境因素。我们得出结论，该基因异常在胰岛素抵抗和2型糖尿病的发病机制中不起作用。巴塞尔协议。
We investigated the relationship of codon 972 polymorphism of the insulin receptor substrate-1 (IRS-1) gene with insulin resistance in the Japanese population. Among 130 patients with type-2 diabetes mellitus (DM), we identified 6 who were heterozygous for the Gly972Arg mutation. Among 744 healthy subjects, 6 were heterozygous and 1 was homozygous for the mutation. A hyperinsulinemic euglycemic clamp study was performed in 3 of 6 diabetic patients with the heterozygous Gly972Arg mutation and in 60 without it. Both groups showed almost the same levels of insulin sensitivity (glucose infusion rate, GIR = 50.2 +/- 3.0 vs. 51.3 +/- 12.1 mu mol/kg/min). Similarly, there was no difference in insulin sensitivity between healthy subjects with and without the mutation using the homeostasis model assessment (HOMA index = 1.14 +/- 0.50 vs. 1.02 +/- 0.63). The frequency of the Gly972Arg allele was not increased in diabetic patients compared with control subjects even in aged (>50 years old) or obese (BMI greater than or equal to 25) subjects. Among healthy subjects, we identified a 25-year-old male with the homozygous Gly972Arg allele. He was slightly obese (BMI = 25.5) but showed relatively high insulin sensitivity, almost equal to that of healthy subjects without the mutation (GIR = 67.2 vs. 71.8 +/- 22.0 mu mol/kg/min). Because the GIR in healthy subjects was significantly higher compared with that in type-2 DM patients, we speculate that another genetic or environmental factor producing a more deleterious effect on insulin sensitivity may exist in diabetic patients. We conclude that this gene abnormality does not play a role in the pathogenesis of insulin resistance and type-2 DM. Copyright (C) 2000 S. Karger AG. Basel.