Blockade of IRS1 in isolated rat pancreatic islets improves glucose‐induced insulin secretion

FEBS Letters

Magalhães, Everardo C²  Ferreira, Fabiano²  Souza, Cláudio T¹  Bordin, Silvana³  Saad, Mario J.A¹  Boschero, Antonio C²  Araujo, Eliana P²  Velloso, Lı́cio A¹  Amaral, Maria E.C² 

[1] Department of Internal Medicine, University of Campinas, Campinas, Brazil;Department of Physiology and Biophysics, University of Campinas, Campinas, Brazil;Department of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil

关键词: Insulin;    Insulin receptor;    Insulin receptor substrate-1;    Glucagon;    Somatostatin;   

DOI  :  10.1016/S0014-5793(02)03580-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Several neural, hormonal and biochemical inputs actively participate in the balance of insulin secretion induced by blood glucose fluctuations. The exact role of insulin as an autocrine and paracrine participant in the control of its own secretion remains to be determined, mostly due to insufficient knowledge about the molecular phenomena that govern insulin signaling in pancreatic islets. In the present experiments we demonstrate that higher insulin receptor and insulin receptor substrates-1 and -2 (IRS1 and IRS2) concentrations are predominantly encountered in cells of the periphery of rat pancreatic islets, as compared to centrally located cells, and that partial blockade of IRS1 protein expression by antisense oligonucleotide treatment leads to improved insulin secretion induced by glucose overload, which is accompanied by lower steady-state glucagon secretion and blunted glucose-induced glucagon fall. These data reinforce the inhibitory role of insulin upon its own secretion in isolated, undisrupted pancreatic islets.

【 授权许可】

Unknown