INSULIN-RESISTANCE - INTERACTIONS BETWEEN OBESITY AND A COMMON VARIANT OF INSULIN-RECEPTOR SUBSTRATE-1
INSULIN-RESISTANCE - INTERACTIONS BETWEEN OBESITY AND A COMMON VARIANT OF INSULIN-RECEPTOR SUBSTRATE-1
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DOI：
10.1016/s0140-6736(95)92779-4
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发表时间：
1995-08-12
期刊：
影响因子：
168.9
通讯作者：
PEDERSEN, O
中科院分区：
文献类型：
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作者：
CLAUSEN, JO;HANSEN, T;PEDERSEN, O
我们以前发现了两个氨基酸多态性的密码子513和972的蛋白质胰岛素受体底物-1（IRS-1），这是重要的细胞胰岛素作用。我们研究了这些多态性是否与胰岛素敏感性的变化有关，随机抽取了380名年龄在18-32岁的无血缘关系的白色受试者，在静脉葡萄糖和甲苯磺丁脲耐量试验中测量了胰岛素敏感性和分泌。采用构象多态性和酶切方法检测IRS-1基因多态性。没有发现密码子-513变异的纯合子携带者，但一名非肥胖男性在两个等位基因上都有密码子-972突变。他空腹血清胰岛素和C肽浓度低，胰岛素敏感性和葡萄糖有效性低。在24小时地塞米松试验期间，患者出现一过性糖尿病。IRS-1的密码子-513和密码子-972变异体在3%和9%的受试者中发现。任一多态性的非肥胖携带者与非肥胖野生型受试者（没有已知的IRS-1变体）具有相似的胰岛素敏感性和胰腺β细胞功能。然而，方差分析显示，肥胖（体重指数大于或等于25 kg/m2）和密码子972变异体的杂合形式之间存在显著的相互作用（p
We previously discovered two aminoacid polymorphisms in codons 513 and 972 of the protein insulin receptor substrate-1 (IRS-1), which is important in cellular insulin action. We have investigated whether these polymorphisms are associated with changes in insulin sensitivity in a random sample of young healthy adults.Insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test in 380 unrelated white subjects aged 18-32. IRS-1 polymorphisms were examined conformation polymorphism and enzyme digestion. No homozygous carrier of the codon-513 variant was identified, but one non-obese man had the codon-972 mutation on both alleles. He had low fasting-serum insulin and C-peptide concentrations and low insulin sensitivity and glucose effectiveness. During a 24 h dexamethasone test, he developed transient diabetes. In their heterozygous forms the codon-513 and codon-972 variants of IRS-1 were found in 3% and 9% of the subjects. Non-obese carriers of either polymorphism had similar insulin sensitivity and pancreatic beta-cell function to non-obese wild-type subjects (no known variants of IRS-1). Analysis of variance showed, however, a significant interaction between obesity (body-mass index greater than or equal to 25 kg/m(2)) and the heterozygous form of the codon-972 variant (p