Denley A, Wallace J C, Cosgrove L J, Forbes B E
School of Molecular and Biomedical Sciences, The University of Adelaide, Adelaide 5005, South Australia.
Horm Metab Res. 2003 Nov-Dec;35(11-12):778-85. doi: 10.1055/s-2004-814157.
The insulin receptor plays a vital role in mediating the actions of insulin. These include metabolic and mitogenic effects. This review will focus on the role of the insulin receptor isoforms in normal development and the pathogenesis of certain cancers and type 2 diabetes. There are two insulin receptor isoforms arising from the alternative splicing of exon 11 resulting in either the exon 11+ (IR-B) isoform (including 12 amino acids encoded by exon 11) or the exon 11- (IR-A) isoform. The isoforms have different affinities for insulin, IGF-II and IGF-I with the exon 11- isoform binding both insulin and IGF-II with high affinities. Interestingly, differential expression of the insulin receptor isoforms has been demonstrated in disease. Several cancer cell types that also overexpress IGF-II preferentially express the exon 11- isoform. Activation of the exon 11- insulin receptor by IGF-II and insulin results in mitogenic effects and a potentiation of the cancer phenotype. Also hyperinsulinemia has been associated with increased risk of cancer. Differential expression of the insulin receptor isoforms has also been demonstrated in type 2 diabetes although there is some discrepancy in the literature as to which isoform is expressed.
胰岛素受体在介导胰岛素的作用中起着至关重要的作用。这些作用包括代谢和促有丝分裂效应。本综述将聚焦于胰岛素受体异构体在正常发育以及某些癌症和2型糖尿病发病机制中的作用。由于外显子11的可变剪接产生了两种胰岛素受体异构体，即外显子11+(IR-B)异构体（包括由外显子11编码的12个氨基酸）或外显子11-(IR-A)异构体。这些异构体对胰岛素、IGF-II和IGF-I具有不同的亲和力，外显子11-异构体对胰岛素和IGF-II均具有高亲和力。有趣的是，在疾病中已证实胰岛素受体异构体存在差异表达。几种同时过表达IGF-II的癌细胞类型优先表达外显子11-异构体。IGF-II和胰岛素对外显子11-胰岛素受体的激活会导致促有丝分裂效应并增强癌症表型。此外，高胰岛素血症与癌症风险增加有关。尽管关于在2型糖尿病中表达哪种异构体，文献中存在一些差异，但胰岛素受体异构体的差异表达在2型糖尿病中也已得到证实。
