ROS constitute a convergence nexus in the development of IGF1 resistance and impaired wound healing in a rat model of type 2 diabetes.

Disease Models & Mechanisms
Milad S Bitar, Fahd Al-Mulla

Abstract

An indolent non-healing wound and insulin and/or insulin-like growth factor (IGF1) resistance are cardinal features of diabetes, inflammation and hypercortisolemia. Little is known about why these phenomena occur in so many contexts. Do the various triggers that induce insulin and/or IGF1 resistance and retard wound healing act through a common mechanism? Cultured dermal fibroblasts from rats and full-thickness excisional wounds were used as models to test the premise that reactive oxygen species (ROS) play a causal role in the development of IGF1 resistance and impaired wound healing under different but pathophysiologically relevant clinical settings, including diabetes, dexamethasone-induced hypercortisolemia and TNFα-induced inflammation. In normal fibroblasts, IGF1 initiated a strong degree of phosphorylation of insulin receptor substrate 1 (IRS1) (Tyr612) and Akt (Ser473), concomitantly with increased PI3K activity. This phenomenon seemed to be attenuated in fibroblasts that had phenotypic features of diabetes, inflammation or hypercortisolemia. Notably, these cells also exhibited an increase in the activity of the ROS-phospho-JNK (p-JNK)-p-IRS1 (Ser307) axis. The above-mentioned defects were reflected functionally by atte...Continue Reading

References

Dec 1, 1992·The British Journal of Surgery·J L McCallB R Parry
May 1, 1995·The Journal of Clinical Investigation·G S HotamisligilB M Spiegelman
Apr 1, 1996·Journal of Pharmacological and Toxicological Methods·H XieW W Lautt
Aug 1, 1997·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·M S Bitar
Jan 27, 1999·Methods in Enzymology·C C Winterbourn, I H Buss
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y RongM Baudry
Nov 15, 2000·Canadian Journal of Physiology and Pharmacology·P Sadri, W W Lautt
Dec 21, 2000·American Journal of Physiology. Cell Physiology·D A SiwikW S Colucci
Jul 12, 2002·American Journal of Physiology. Endocrinology and Metabolism·C SeverinoG Tonolo
Oct 26, 2002·Free Radical Biology & Medicine·Gustavo Barja
Nov 6, 2002·The Journal of Biological Chemistry·Yong Hee LeeMorris F White
Nov 26, 2002·Nature·Jiro HirosumiGökhan S Hotamisligil
Jan 1, 2003·Genes, Chromosomes & Cancer·Haim Werner, Charles T Roberts
Aug 7, 2003·Current Opinion in Pharmacology·Brydon L BennettAlan J Lewis
Aug 9, 2003·Critical Care Medicine·Dean Thomas Williams, Keith Harding
May 12, 2004·Current Medicinal Chemistry·A R SmithT M Hagen
Aug 25, 2004·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·M S BitarF Al-Mulla
Sep 2, 2004·European Journal of Endocrinology·Paul J Jenkins, Stephen A Bustin
May 3, 2005·The Journal of Clinical Investigation·Kathryn E Wellen, Gökhan S Hotamisligil
Jun 29, 2005·Diabetes·Jiang ChenAngelika Bierhaus
Jul 5, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gürol TuncmanGökhan S Hotamisligil
Sep 26, 2006·Canadian Journal of Physiology and Pharmacology·Morris F White
Feb 15, 2007·The Journal of Investigative Dermatology·Sabine A EmingJeffrey M Davidson
Nov 1, 2007·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Diana H YuDavid M Young
Jan 8, 2008·Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]·Monica De MatteiPaolo Zamboni
Feb 6, 2008·Biochimica Et Biophysica Acta·Chandan K Sen, Sashwati Roy
Mar 8, 2008·The Journal of Investigative Dermatology·Andreea M BujorMaria Trojanowska
Mar 21, 2008·QJM : Monthly Journal of the Association of Physicians·M P KhanolkarJ W Stephens
Jul 17, 2008·Nature Reviews. Molecular Cell Biology·Matthias Schäfer, Sabine Werner
Dec 2, 2008·Biochimica Et Biophysica Acta·Sara FröjdöLuciano Pirola
Dec 6, 2008·Biology of the Cell·Robert J Cain, Anne J Ridley
Jan 16, 2009·Diabetes/metabolism Research and Reviews·Swapnil N RajpathakHoward D Strickler
Mar 3, 2009·Vitamins and Hormones·Sigalit Boura-Halfon, Yehiel Zick
Aug 4, 2009·Respirology : Official Journal of the Asian Pacific Society of Respirology·Veneta L ShopovaAngelina M Stoyanova

❮ Previous
Next ❯

Citations

Nov 2, 2012·Fibrogenesis & Tissue Repair·Michael P Czubryt
Nov 21, 2013·Acta Neuropathologica Communications·Caleb W GroteDouglas E Wright
Dec 5, 2012·Endocrine-related Cancer·Sefirin DjioguePaul Faustin Seke Etet
Jan 6, 2015·Iranian Red Crescent Medical Journal·Fereshteh Talebpour AmiriNariman Mosaffa
Nov 6, 2012·Cellular Signalling·Maulilio John KipanyulaArmel Hervé Nwabo Kamdje
Jan 30, 2013·Journal of Cellular Physiology·Fahd Al-MullaKam C Yeung
Sep 23, 2016·Archives of Dermatological Research·T EmanuelliE Carvalho
Dec 29, 2016·Antioxidants & Redox Signaling·Emmeran Le MoalRémi Mounier
Dec 19, 2014·EMBO Molecular Medicine·Karmveer SinghKarin Scharffetter-Kochanek
Sep 15, 2017·Interdisciplinary Sciences, Computational Life Sciences·Mathew SaumyaT V Suchithra
Dec 17, 2014·Expert Review of Anticancer Therapy·Khan ShahanavajChristian Rolfo
May 11, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Morteza Najaf Zadeh GharaboghazShahram Saghaie

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR
transfection
immunoprecipitation
electrophoresis
Assay
FCS
amputations
amputation

Software Mentioned

Adobe
Adobe PhotoShop

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.