Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose disposal in response to insulin is impaired. We have developed a transgenic mouse with a dominant-negative insulin-like growth factor-I receptor (KR-IGF-IR) specifically targeted to the skeletal muscle. Expression of KR-IGF-IR resulted in the formation of hybrid receptors between the mutant and the endogenous IGF-I and insulin receptors, thereby abrogating the normal function of these receptors and leading to insulin resistance. Pancreatic beta-cell dysfunction developed at a relative early age, resulting in diabetes. These mice provide an excellent model to study the molecular mechanisms underlying the development of human type 2 diabetes.

中文翻译：

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骨骼肌中IGF-1和胰岛素受体的功能失活会导致2型糖尿病。

周围胰岛素抵抗和胰岛素作用受损是2型糖尿病的主要特征。该主要疾病的第一个可观察到的缺陷发生在肌肉中，其中葡萄糖对胰岛素的响应受到损害。我们已经开发了具有显着负性胰岛素样生长因子-I受体（KR-IGF-IR）的转基因小鼠，专门针对骨骼肌。KR-IGF-1R的表达导致在突变体与内源性IGF-1和胰岛素受体之间形成杂交受体，从而废除了这些受体的正常功能并导致胰岛素抵抗。胰腺β细胞功能障碍在相对早期发展，导致糖尿病。这些小鼠为研究人类2型糖尿病发展的分子机制提供了一个极好的模型。