Effects of cell-permeable ceramides and tumor necrosis factor-alpha on insulin signaling and glucose uptake in 3T3-L1 adipocytes

Diabetes
C N WangD N Brindley

Abstract

Incubation of 3T3-L1 adipocytes with C2- and C6-ceramides (N-acetyl- and N-hexanoylsphingosines) but not dihydro-C2-ceramide increased 2-deoxyglucose uptake in the absence of insulin. This effect was inhibited by PD 98059, LY 294002, and rapamycin, which block the activation of mitogen-activated protein kinase, phosphatidylinositol (PI) 3-kinase, and ribosomal S6 kinase, respectively. Long-term increases in PI 3-kinase activity associated with insulin receptor substrate 1 (IRS-1) increased GLUT1 and GLUT4 concentrations in plasma membranes. This together with increased GLUT1 (but not GLUT4) synthesis explains the increase in non-insulin-dependent glucose uptake. C2-ceramide inhibited insulin-stimulated glucose uptake after 2 h by decreasing insulin-induced translocation of GLUT1 and GLUT4 to plasma membranes. This occurred when there was no increase in basal glucose uptake or decrease in activation of IRS-1 or PI 3-kinase. Incubation for 24 h with tumor necrosis factor-alpha (TNF-alpha) but not C2-ceramide decreased the concentration and insulin-induced tyrosine phosphorylation of IRS-1 in this experimental system. Cell-permeable ceramides mimic some effects of TNF-alpha, especially in stimulating basal glucose uptake. We ident...Continue Reading

Citations

Nov 15, 2002·Trends in Endocrinology and Metabolism : TEM·Eileen L WhitemanMorris J Birnbaum
Jul 30, 1999·Biochimica Et Biophysica Acta·D W WaggonerD N Brindley
Apr 12, 2000·Journal of the American College of Nutrition·J Schrezenmeir, A Jagla
Apr 9, 2013·Optometry and Vision Science : Official Publication of the American Academy of Optometry·Sarah KimHyun Ki Lee
Jan 19, 2005·Acta Physiologica Scandinavica·A M ValverdeM Lorenzo
Jun 8, 2000·Annals of the New York Academy of Sciences·S A SummersM J Birnbaum
Aug 17, 2011·Molecular and Cellular Biology·Zhiqiang LiXian-Cheng Jiang
Jul 10, 2013·Lipids in Health and Disease·Sehamuddin GaladariFaisal Thayyullathil
Mar 11, 2000·Journal of Pediatric Endocrinology & Metabolism : JPEM·A TiroshN Bashan
Jun 13, 2008·The Review of Diabetic Studies : RDS·Marek Straczkowski, Irina Kowalska
Feb 13, 2001·Biochemical and Biophysical Research Communications·M J ZindaM T Lai
Oct 6, 2001·Biochemical and Biophysical Research Communications·R J Grigsby, R T Dobrowsky
Nov 26, 2013·Mechanisms of Ageing and Development·Kavita S JadhavDavid L Williamson
Sep 21, 2001·Biochemical and Biophysical Research Communications·S GoetzeE Fleck
Dec 17, 2014·Current Problems in Cardiology·Alessandra Dei CasJaved Butler
Nov 11, 2008·Brain Research Reviews·Gonzalo ArboledaHumberto Arboleda
Jun 16, 2009·Molecular and Cellular Endocrinology·Eugene ChangDorothy Teegarden
May 9, 2012·Cell Metabolism·Jose A Chavez, Scott A Summers
Jan 28, 2010·American Journal of Physiology. Endocrinology and Metabolism·David N BrindleyJason R B Dyck
Feb 18, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·A Brianne ThrushDavid J Dyck
Aug 2, 2018·Physiological Reviews·Max C Petersen, Gerald I Shulman
Mar 24, 2020·The Biochemical Journal·Nicole G BarraJonathan D Schertzer

❮ Previous
Next ❯

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.

American Diabetes Association Journals

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