Inactivation of muscle insulin and IGF-I receptors and insulin responsiveness
Inactivation of muscle insulin and IGF-I receptors and insulin responsiveness
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DOI：
10.1097/00075197-200207000-00004
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发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
Accili, D
中科院分区：
文献类型：
--
作者：
Le Roith, D;Kim, H;Accili, D
目的的审查这篇综述将概述该地区的胰岛素刺激的骨骼肌葡萄糖摄取及其对全身葡萄糖稳态的影响的最新进展，使用基因缺失和转基因mouse models.Recent findings胰岛素抵抗往往是第一个异常检测的情况下，2型糖尿病，并被认为是在周围组织，特别是肌肉的水平。胰岛素受体和胰岛素样生长因子I受体都能够刺激骨骼肌摄取葡萄糖。一种模型涉及肌肉葡萄糖转运蛋白4的基因缺失，这导致严重的胰岛素抵抗和高血糖症，第二种模型使用转基因方法消除胰岛素样生长因子I受体和胰岛素受体的功能，导致严重的胰岛素抵抗和糖尿病的进展。两种模型都证明，胰岛素样生长因子I受体和胰岛素受体或共同信号传导途径的消除必须被抑制，以引起足够的胰岛素抵抗，从而导致2型糖尿病;其中葡萄糖毒性或脂毒性参与了从严重到抵抗完全成熟的2型糖尿病的进展。因此，骨骼肌中胰岛素刺激的葡萄糖摄取的消除，至少在小鼠中，可能导致严重的胰岛素抵抗和糖尿病。
Purpose of review This review will outline the recent advances in the area of insulin-stimulated skeletal muscle glucose uptake and its effect on whole body glucose homeostasis, using gene-deletion and transgenic mouse models.Recent findings Insulin resistance is often the first abnormality detected in cases of type 2 diabetes, and is seen at the level of the peripheral tissues especially muscle. Both the insulin receptor and the insulin-like growth factor I receptor are capable of stimulating glucose uptake into skeletal muscle. One model involves the gene deletion of muscle glucose transport protein 4, which leads to severe insulin resistance and hyperglycemia, and a second model using a transgenic approach abrogates the function of the insulin-like growth factor I receptor and the insulin receptor resulting in severe insulin resistance and progression to diabetes. Both models demonstrate that abrogation of the insulin-like growth factor I receptor and the insulin receptor or a common signalling pathway must be inhibited to cause sufficient insulin resistance to lead to type 2 diabetes; with either glucotoxicity or lipotoxicity being involved in the progression from severe to resistance to full-blown type 2 diabetes.Summary Thus, abrogation of insulin-stimulated glucose uptake in skeletal muscle, at least in mice, may lead to severe insulin resistance and diabetes.