Reactive oxygen species have a causal role in multiple forms of insulin resistance

Nature
Nicholas HoustisEric S Lander

Abstract

Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that incre...Continue Reading

References

Dec 1, 1992·The British Journal of Surgery·J L McCallB R Parry
Apr 1, 1982·The Journal of Trauma·G M VaughanA D Mason
Jan 1, 1983·The British Journal of Surgery·H B StonerE Gross
May 1, 1995·The Journal of Clinical Investigation·G S HotamisligilB M Spiegelman
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·G S HotamisligilB M Spiegelman
Apr 26, 1997·Lancet·I J BujalskaP M Stewart
Jun 1, 2000·Biochemistry·M Di PaolaM Lorusso
Jun 22, 2000·Archives of Biochemistry and Biophysics·S YangA M Diehl
Feb 14, 2002·Archives of Biochemistry and Biophysics·Hadi MoiniLester Packer
Jun 28, 2002·Diabetes·John P KirwanPatrick M Catalano
Nov 26, 2002·Nature·Jiro HirosumiGökhan S Hotamisligil
Oct 15, 2003·The Journal of Clinical Endocrinology and Metabolism·Hideki UrakawaYukihiko Adachi
Sep 28, 2004·Nature Medicine·Hideaki KanetoMasatsugu Hori
Nov 13, 2004·The Journal of Biological Chemistry·Ying LinPhilipp E Scherer
Dec 16, 2004·The Journal of Clinical Investigation·Shigetada FurukawaIichiro Shimomura
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov

❮ Previous
Next ❯

Citations

Jul 10, 2007·Journal of Physiology and Biochemistry·J A Martínez
Jan 10, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Hongming MiaoLixia Gan
May 15, 2010·Herz·Bernd StratmannDiethelm Tschoepe
Jun 6, 2006·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·Mark Berneburg
Sep 6, 2012·Applied Microbiology and Biotechnology·Yi QiaoYonghui Shi
Apr 2, 2008·Cell and Tissue Research·D L RibeiroR M Góes
Jan 20, 2009·Cell Biology and Toxicology·Marjolaine RocheEmmanuel Bourdon
Aug 30, 2008·Reviews in Endocrine & Metabolic Disorders·Anuradha Vivekanadan-GiriSubramaniam Pennathur
Mar 9, 2013·Frontiers of Medicine·Jianping Ye
Aug 2, 2006·Current Diabetes Reports·Michaela Diamant, Maarten E Tushuizen
Feb 5, 2009·Current Diabetes Reports·Craig Lawrence Kien
Mar 20, 2013·Current Heart Failure Reports·Konstantinos Drosatos, P Christian Schulze
Dec 28, 2011·Biological Trace Element Research·Hui Chen, Chao Tan
Oct 1, 2009·Indian Journal of Clinical Biochemistry : IJCB·P P SinghPraveen Sharma
Jul 7, 2011·Indian Journal of Clinical Biochemistry : IJCB·P P SinghPraveen Sharma
Mar 24, 2012·Neurotoxicity Research·Yan Zhou, William L Klein
Feb 22, 2012·Journal of Physiology and Biochemistry·Isabel Bondia-PonsJ Alfredo Martinez
Mar 26, 2013·Molecular and Cellular Endocrinology·Taiyi KuoJen-Chywan Wang
Apr 10, 2008·The British Journal of Nutrition·Paul TrayhurnI Stuart Wood
Apr 27, 2010·The British Journal of Nutrition·Inka BoomgaardenFrank Döring
May 23, 2013·The British Journal of Nutrition·Raffaella CrescenzoSusanna Iossa
Aug 25, 2009·The Proceedings of the Nutrition Society·I Stuart WoodPaul Trayhurn
Jul 28, 2009·International Psychogeriatrics·Ahmet Turan Isik, Ergun Bozoglu
Aug 13, 2011·Accounts of Chemical Research·Alexander R LippertChristopher J Chang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.

Related Papers

Antioxidants & Redox Signaling
Joseph L EvansIra D Goldfine
Proceedings of the National Academy of Sciences of the United States of America
Kyle L HoehnDavid E James
© 2022 Meta ULC. All rights reserved