Insulin receptor isoform A confers a higher proliferative capability to pancreatic beta cells enabling glucose availability and IGF-I signaling

Molecular and Cellular Endocrinology
Óscar EscribanoManuel Benito

Abstract

The main compensatory response to insulin resistance is the pancreatic beta cell hyperplasia to account for increased insulin secretion. In fact, in a previous work we proposed a liver-pancreas endocrine axis with IGF-I (insulin-like growth factor type I) secreted by the liver acting on IRA insulin receptor in beta cells from iLIRKO mice (inducible Liver Insulin Receptor KnockOut) that showed a high IRA/IRB ratio. However, the role of insulin receptor isoforms in the IGF-I-induced beta cell proliferation as well as the underlying molecular mechanisms remain poorly understood. For this purpose, we have used four immortalized mouse beta cell lines: bearing IR (IRLoxP), lacking IR (IRKO), expressing exclusively IRA (IRA), or alternatively expressing IRB (IRB). Pancreatic beta cell proliferation studies showed that IRA cells are more sensitive than those expressing IRB to the mitogenic response induced by IGF-I, acting through the pathway IRA/IRS-1/2/αp85/Akt/mTORC1/p70S6K. More importantly, IRA beta cells, but not IRB, showed an increased glucose uptake as compared with IRLoxP cells, this effect being likely owing to an enhanced association between Glut-1 and Glut-2 with IRA. Overall, our results strongly suggest a prevalent role ...Continue Reading

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Citations

Apr 24, 2016·Cellular Oncology (Dordrecht)·Luis Antonio Flores-LópezLuis Arturo Baiza-Gutman
Dec 5, 2017·Journal of Diabetes Research·O EscribanoA Gómez-Hernández
Aug 27, 2016·Disease Models & Mechanisms·Sabela Diaz-CastroverdeManuel Benito
Aug 15, 2018·American Journal of Physiology. Endocrinology and Metabolism·Maxim D SeferovicMaureen Gannon
Oct 4, 2017·Endocrine Reviews·Antonino BelfioreRiccardo Vigneri
Mar 9, 2017·American Journal of Physiology. Endocrinology and Metabolism·Abdul Bari MuhammadXianxin Hua
Sep 10, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jiayue YangStephen J Pandol
Sep 4, 2018·Frontiers in Physiology·Natalia de Las HerasAlmudena Gómez-Hernández

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