Transgenic mice overexpressing human G972R IRS-1 show impaired insulin action and insulin secretion.

Journal of Cellular and Molecular Medicine
M L HribalM Federici

Abstract

Molecular scanning of human insulin receptor substrate (Irs) genes revealed a single lrs1 prevalent variant, a glycine to arginine change at codon 972 (G972R); previous in vitro studies had demonstrated that the presence of this variant results in an impaired activation of the insulin signalling pathway, while human studies gave controversial results regarding its role in the pathogenesis of insulin resistance and related diseases. To address in vivo impact of this IRS-1 variant on whole body glucose homeostasis and insulin signalling, we have generated transgenic mice overexpressing it (Tg972) and evaluated insulin action in the liver, skeletal muscle and adipose tissue and assessed glucose homeostasis both under a normal diet and a high-fat diet. We found that Tg972 mice developed age-related glucose and insulin intolerance and hyperglycaemia, with insulin levels comparatively low. Glucose utilization and insulin signalling were impaired in all key insulin target tissues in Tg972 mice. There were no differences in pancreatic morphology between Tg972 and wild-type mice, however when insulin secretion was evaluated in isolated islets, it was significantly reduced in Tg972 mice islets at any glucose concentration tested. Under a...Continue Reading

References

Aug 3, 1999·The Journal of Clinical Investigation·O PorzioG Sesti
Dec 22, 1999·The Journal of Clinical Investigation·R N KulkarniC R Kahn
Dec 2, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M FedericiG Sesti
Oct 20, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G SestiR Lauro
Jun 24, 2004·Diabetic Medicine : a Journal of the British Diabetic Association·R M van DamE J M Feskens
Feb 18, 2006·The Journal of Clinical Investigation·Haruka OkamotoDomenico Accili
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Cullen M TaniguchiC Ronald Kahn
May 12, 2006·The Journal of Biological Chemistry·Tonya L MartinBarbara B Kahn
Aug 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Otto TschritterAndreas Fritsche
Dec 26, 2006·The Journal of Clinical Investigation·Tanya HansotiaDaniel J Drucker
Jan 30, 2007·Clinical Pharmacology and Therapeutics·J Woodcock
Jun 16, 2007·PLoS Medicine·Valeriya LyssenkoUNKNOWN Botnia Study Group

❮ Previous
Next ❯

Citations

Sep 29, 2012·Molecular Diagnosis & Therapy·Gaia Chiara Mannino, Giorgio Sesti
Jan 22, 2009·Médecine sciences : M/S·Franck PeirettiGilles Nalbone
Jun 26, 2012·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Yuan C DingUNKNOWN Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA)
Jun 24, 2010·Journal of Cellular and Molecular Medicine·Anita M HennigeHans-Ulrich Häring
Jul 12, 2017·The Pharmacogenomics Journal·S PrudenteV Trischitta
Nov 20, 2009·Nature Reviews. Endocrinology·Sabrina PrudenteVincenzo Trischitta
Aug 9, 2011·Expert Review of Proteomics·Jian-Ying ZhouWei-Jun Qian
Oct 21, 2015·Hormone Molecular Biology and Clinical Investigation·Atul S Deshmukh
May 16, 2020·International Journal of Endocrinology·Juyi LiAiping Deng
Nov 25, 2018·International Journal of Molecular Sciences·Laura NigiGuido Sebastiani
Sep 10, 2019·European Journal of Pharmacology·Bhoomika M Patel, Ramesh K Goyal

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping
PCR
ELISA
transgenic
immunoprecipitation

Related Concepts

Related Feeds

Asprosin

Asprosin is a fasting-induced hormone produced in the white adipose tissue to stimulate the hepatic release of glucose into the bloodstream. Discover the latest research on this protein hormone here.