In vivo mutagenesis of the insulin receptor.

The Journal of Biological Chemistry
Haruka Okamoto, Domenico Accili

Abstract

Mice bearing targeted gene mutations that affect insulin receptor (Insr) function have contributed important new information on the pathogenesis of type 2 diabetes. Whereas complete Insr ablation is lethal, conditional mutagenesis in selected tissues has more limited consequences on metabolism. Studies of mice with tissue-specific ablation of Insr have indicated that both canonical (e.g. muscle and adipose tissue) and noncanonical (e.g. liver, pancreatic beta-cells, and brain) insulin target tissues can contribute to insulin resistance, albeit in a pathogenically distinct fashion. Furthermore, experimental crosses of Insr mutants with mice carrying mutations that affect insulin action at more distal steps of the insulin signaling cascade have begun to unravel the genetics of type 2 diabetes. These studies are consistent with an oligogenic inheritance, in which synergistic interactions among few alleles may account for the genetic susceptibility to diabetes. In addition to mutant alleles conferring an increased risk of diabetes, these studies have uncovered mutations that protect against insulin resistance, thus providing proof-of-principle for the notion that certain alleles may confer resistance to diabetes.

References

Jun 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D Accili, S I Taylor
Jan 1, 1996·Annual Review of Medicine·S Ghosh, F S Collins
Mar 12, 1998·Nature·D J WithersM F White
Sep 3, 1998·Diabetologia·D PorteM W Schwartz
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·L GuarenteR Amasino
Dec 3, 1999·European Journal of Clinical Investigation·E FerranniniA Natali
Dec 22, 1999·The Journal of Clinical Investigation·R N KulkarniC R Kahn
Jan 22, 2000·The Journal of Clinical Investigation·Y KidoD Accili
Sep 21, 2000·The Journal of Biological Chemistry·S F PrevisG I Shulman
Oct 24, 2000·Trends in Endocrinology and Metabolism : TEM·M A Permutt, A T Hattersley
May 5, 2001·Cell·C Kenyon
Dec 6, 2001·The Journal of Clinical Investigation·D Accili
Dec 12, 2001·Endocrine Reviews·J NakaeD Accili
May 22, 2002·Nature Neuroscience·Silvana ObiciLuciano Rossetti

❮ Previous
Next ❯

Citations

Oct 23, 2003·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Edward J Masoro
Mar 11, 2009·The Journal of Clinical Investigation·Seongah HanAlan R Tall
Sep 28, 2010·Ageing Research Reviews·Elad Ziv, Donglei Hu
Mar 25, 2005·Diabetic Medicine : a Journal of the British Diabetic Association·D A Rees, J C Alcolado
Jun 6, 2009·Aging Cell·Ludmila PawlikowskaUNKNOWN Study of Osteoporotic Fractures
Jan 23, 2008·Aging Cell·Maris KuningasRudi G J Westendorp
Jun 29, 2012·Journal of Cellular Physiology·Saori Morino-KogaHirofumi Kai
Nov 23, 2012·Diabetes·Andrew Ward
Jul 4, 2006·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Stephen C WoodsWolfgang Langhans

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.