Pioglitazone ameliorates tumor necrosis factor-alpha-induced insulin resistance by a mechanism independent of adipogenic activity of peroxisome proliferator--activated receptor-gamma

Diabetes
M IwataM Kobayashi

Abstract

Tumor necrosis factor (TNF)-alpha is one of the candidate mediators of insulin resistance associated with obesity, a major risk factor for the development of type 2 diabetes. The insulin resistance induced by TNF-alpha is antagonized by thiazolidinediones (TZDs), a new class of insulin-sensitizing drugs. The aim of the current study was to dissect the mechanism whereby pioglitazone, one of the TZDs, ameliorates TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes. Pioglitazone restored insulin-stimulated 2-deoxyglucose (DOG) uptake, which was reduced by TNF-alpha, with concomitant restorations in tyrosine phosphorylation and protein levels of insulin receptor (IR) and insulin receptor substrate (IRS)-1, as well as association of the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase with IRS-1 and PI 3-kinase activity. Adenovirus-mediated gene transfer of either wild-type human peroxisome proliferator-activated receptor (PPAR)-gamma2 or a mutant carrying a replacement at the consensus mitogen-activated protein kinase phosphorylation site (hPPAR-gamma2-S112A) promoted adipogenesis of 3T3-L1 fibroblasts and restored TNF-alpha-induced decrease of triglyceride in adipocytes as effectively as pioglitazone. Overexpress...Continue Reading

References

Jan 1, 1992·Annual Review of Immunology·P Vassalli
Nov 24, 1995·The Journal of Biological Chemistry·T HarutaJ M Olefsky
Jan 28, 1994·Biochemical and Biophysical Research Communications·K M Rice, C W Garner
Apr 6, 1995·Biochemical and Biophysical Research Communications·K KotaniM Kasuga
Nov 1, 1994·Diabetes·G S Hotamisligil, B M Spiegelman
Nov 3, 1994·The New England Journal of Medicine·J J NolanJ Olefsky
Aug 1, 1994·Metabolism: Clinical and Experimental·I M el-KebbiR J Pollet
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·G S HotamisligilB M Spiegelman
Dec 15, 1995·Cell·D J MangelsdorfR M Evans
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·C B Kallen, M A Lazar
Oct 6, 1997·The Journal of Clinical Investigation·P PeraldiB M Spiegelman
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·J L OberfieldT M Willson
Feb 17, 2000·The Journal of Clinical Investigation·P D MilesJ M Olefsky

❮ Previous
Next ❯

Citations

Dec 18, 2001·Diabetes/metabolism Research and Reviews·B NazlielB Koçer
Feb 21, 2006·Diabetologia·H RichardsonW M Macfarlane
Sep 3, 2003·Biochemical and Biophysical Research Communications·M ShibasakiY Saito
Apr 13, 2010·Diabetes, Obesity & Metabolism·S FukudaM Matsushita
Jun 11, 2002·Annual Review of Nutrition·Frédéric Picard, Johan Auwerx
Jan 9, 2003·Annual Review of Physiology·Gordon A FrancisJohan Auwerx
Jul 3, 2002·Drugs·Fabrice M A C MartensTon J Rabelink
Aug 21, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Si-Zeng Chen, Jian-Dong Xiao
Nov 27, 2007·FEBS Letters·William P Cawthorn, Jaswinder K Sethi
Jan 30, 2016·Trends in Cell Biology·Sona KangEvan D Rosen
Dec 30, 2010·The Journal of Nutritional Biochemistry·Choon Young KimKee-Hong Kim
Dec 2, 2009·Molecular and Cellular Endocrinology·Kalypso Karastergiou, Vidya Mohamed-Ali
Oct 24, 2012·PPAR Research·Ana AlzamendiEduardo Spinedi
Nov 5, 2005·Alimentary Pharmacology & Therapeutics·H ReynaertJ Henrion
Oct 13, 2005·Diabetes, Obesity & Metabolism·C J Bailey
Aug 16, 2003·Clinical Endocrinology·Mark Gurnell
Dec 31, 2011·Journal of Cachexia, Sarcopenia and Muscle·Katja TrobecMitja Lainscak
Apr 28, 2009·Journal of Cellular Biochemistry·Boren JiangYingli Lu
Feb 5, 2003·Biochemical and Biophysical Research Communications·Knut KotarskyBjörn Olde
Nov 29, 2005·Best Practice & Research. Clinical Endocrinology & Metabolism·Mark Gurnell
Dec 31, 2002·Biochemical Pharmacology·Naresh Kumar, Chinmoy S Dey

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.

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.