Analysis of Insulin Receptor Gene in Insulin Resistant Diabetes

胰岛素受体具有内在的酪氨酸激酶活性，对信号转导至关重要。在一个患有A型胰岛素抵抗和黑棘皮病的个体中发现了一个几乎缺乏整个激酶结构域的突变胰岛素受体基因。胰岛素与红细胞或培养成纤维细胞的结合正常。然而，在经eb病毒转化的带前淋巴细胞中部分纯化的胰岛素受体中，受体自磷酸化和酪氨酸激酶对外源性底物的活性降低。与该突变基因相关的胰岛素抵抗是先证者从母亲那里作为显性常染色体显性遗传的。因此，胰岛素受体基因中一个等位基因的缺失可能至少是某些胰岛素抵抗型糖尿病的部分原因。

The insulin receptor has an intrinsic tyrosine kinase activity that is essential for signal transduction. A mutant insulin receptor gene lacking almost the entire kinase domain has been identified in an individual with type A insulin resistance and acanthosis nigricans. Insulin binding to the erythrocytes or cultured fibroblasts from this individual was normal. However receptor autophosphorylation and tyrosine kinase activity toward an exogenous substrate were reduced in partially purified insulin receptors from the preband's lymphocytes that had been transformed by Epstein-Barr virus. The insulin resistance associated with this mutated gene was inherited by the proband from her mother as an apparently autosomal dominant trait. Thus a deletion in one allele of the insulin receptor gene may be at least partly responsible for some instances of insulin-resistant diabetes.