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，这是信号转导所必需的。在一例A型胰岛素抵抗和黑棘皮病患者中发现了一种几乎缺少整个激活区的突变的胰岛素受体基因。胰岛素与此人的红细胞或培养成纤维细胞的结合是正常的。然而，在被EB病毒转化的带前淋巴细胞中，部分纯化的胰岛素受体的受体自磷酸化和对外源底物的酪氨酸激酶活性降低。与这个突变基因相关的胰岛素抵抗是先证者从她母亲那里遗传的，显然是常染色体显性特征。因此，胰岛素受体基因的一个等位基因的缺失可能至少是某些胰岛素抵抗糖尿病的部分原因。

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.