PMID: 15220184Jun 29, 2004Paper

Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic

Diabetes
Domenico Accili

Abstract

Type 2 diabetes arises from a combination of impaired insulin action and defective pancreatic beta-cell function. Classically, the two abnormalities have been viewed as distinct yet mutually detrimental processes. The combination of impaired insulin-dependent glucose metabolism in skeletal muscle and impaired beta-cell function causes an increase of hepatic glucose production, leading to a constellation of tissue abnormalities that has been referred to as the diabetes "ruling triumvirate." Targeted mutagenesis in mice has led to a critical reappraisal of the integrated physiology of insulin action. These studies indicate that insulin resistance in skeletal muscle and adipose tissue does not necessarily lead to hyperglycemia, so long as insulin sensitivity in other tissues is preserved. Additional data suggest a direct role of insulin signaling in beta-cell function and regulation of beta-cell mass, thus raising the possibility that insulin resistance may be the overarching feature of diabetes in all target tissues. I propose that we replace the original picture of a ruling triumvirate with that of a squabbling republic in which every tissue contributes to the onset of the disease.

References

Jun 23, 1979·Lancet·A M LawrenceW A Kokal
Jan 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J L TreadwayJ E Pessin
Apr 1, 1982·The Journal of Clinical Investigation·E A RichterN B Ruderman
Jul 1, 1995·Physiological Reviews·G M Reaven
Jan 1, 1996·Diabetes·S Ghosh, N J Schork
Apr 26, 1996·The Journal of Biological Chemistry·D MassillonL Rossetti
Jan 1, 1996·Annual Review of Medicine·S Ghosh, F S Collins
Sep 13, 1996·Science·N Risch, K Merikangas
Oct 1, 1996·Physiological Reviews·R M O'Brien, D K Granner
May 15, 1997·The Journal of Clinical Investigation·G Di ColaD Accili
Jan 1, 1997·Annual Review of Biochemistry·R W Hanson, L Reshef
Jan 31, 1998·The Journal of Clinical Investigation·S D MittelmanR N Bergman
Mar 12, 1998·Nature·D J WithersM F White
Dec 22, 1999·The Journal of Clinical Investigation·R N KulkarniC R Kahn
Jan 22, 2000·The Journal of Clinical Investigation·Y KidoD Accili
Jun 1, 2000·Journal of Molecular Endocrinology·C J Rhodes
Jun 1, 2000·Endocrinology·S Bonner-Weir
Jul 8, 2000·Proceedings of the National Academy of Sciences of the United States of America·S Bonner-WeirJ J O'Neil
Sep 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·N NasrinM C Alexander-Bridges

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Citations

Dec 21, 2012·Cellular and Molecular Life Sciences : CMLS·Mi Cheong CheongYoung-Ki Paik
Jan 24, 2008·Nature Clinical Practice. Endocrinology & Metabolism·Derek Leroith, Domenico Accili
Aug 2, 2011·Nature Medicine·Utpal B PajvaniDomenico Accili
Nov 2, 2004·Nature Medicine·Domenico Accili, Luca Valenti
Feb 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Clara BoucheAllison B Goldfine
Feb 25, 2010·The Journal of Biological Chemistry·Jose M IrimiaPeter J Roach
Apr 2, 2009·The Journal of Biological Chemistry·Hui-Yu LiuWenhong Cao
Jun 29, 2006·ILAR Journal·Nicole Neubauer, Rohit N Kulkarni
Oct 18, 2008·Diabetes, Obesity & Metabolism·C HinaultR N Kulkarni
Oct 13, 2009·Diabetes, Obesity & Metabolism·C TalchaiD Accili
Mar 26, 2011·Science·Ja Young Kim-Muller, Domenico Accili
Jun 10, 2009·Molecular and Cellular Biology·Tadahiro KitamuraDomenico Accili
Jan 18, 2006·Annual Review of Medicine·Laurie L Baggio, Daniel J Drucker
May 19, 2011·American Journal of Physiology. Endocrinology and Metabolism·Jie NingWenhong Cao
Dec 16, 2010·American Journal of Physiology. Endocrinology and Metabolism·Tao HongWenhong Cao
Jul 30, 2009·American Journal of Physiology. Endocrinology and Metabolism·Hui-Yu LiuWenhong Cao
May 3, 2005·The Journal of Clinical Investigation·Haruka OkamotoLuciano Rossetti
Feb 18, 2006·The Journal of Clinical Investigation·Haruka OkamotoDomenico Accili
Dec 24, 2005·The Journal of Clinical Investigation·Xiaocheng DongMorris F White
Aug 15, 2006·The Journal of Clinical Investigation·Michihiro MatsumotoDomenico Accili
Aug 25, 2007·The Journal of Clinical Investigation·Tadahiro KitamuraDomenico Accili
Dec 30, 2009·The Journal of Clinical Investigation·Marie-Therese RachedStavroula Kousteni
Jul 18, 2009·Molecular Endocrinology·Ushma R JagFrederick M Stanley
Apr 25, 2007·Journal of Pediatric Endocrinology & Metabolism : JPEM·Stefano GhirardelloMohamad Maghnie
Sep 23, 2009·The Journal of Endocrinology·Yi Lin, Zhongjie Sun
May 4, 2011·World Journal of Diabetes·Bhawna Singh, Alpana Saxena
Dec 14, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yan G NiJoseph A Hill
Aug 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Frédéric TremblayAndré Marette
Apr 10, 2007·Proceedings of the National Academy of Sciences of the United States of America·Terumasa OkadaRohit N Kulkarni
Apr 18, 2014·The Journal of Endocrinology·Xuefeng YangWenhong Cao
Oct 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bingning DongDavid D Moore

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