Synergistic activation of mitogen-activated protein kinase by insulin and adenosine triphosphate in liver cells: permissive role of Ca2+

Metabolism: Clinical and Experimental
Pierre S HaddadGérald Van de Werve

Abstract

We have previously demonstrated that insulin and G(q)-coupled receptor agonists individually activate mitogen-activated protein kinase (MAPK) in liver cells and both effects involve an influx of extracellular Ca(2+). Yet, these agonists have opposing physiological actions on hepatocyte glucose metabolism. We thus investigated the interaction between insulin and the P2Y(2) purinergic agonist adenosine triphosphate (ATP) on MAPK in HTC cells, a model hepatocyte cell line, and determined the involvement of cytosolic Ca(2+). Insulin and ATP each induced a dose-dependent phosphorylation of p44/42 MAPK that was partially inhibited by EGTA. However, pretreatment with insulin markedly increased the MAPK phosphorylation response to ATP. This potentiation was canceled by chelation of extracellular Ca(2+) with EGTA. We used patch clamp electrophysiology and fluorescence microscopy to understand the role of intracellular Ca(2+) in this effect. Insulin and ATP, respectively, induced monophasic and multiphasic changes in membrane potential and intracellular Ca(2+) as expected. Pretreatment with 10 nmol/L insulin significantly decreased the initial rapid depolarization (inward nonselective cation current [NSCC]), as well as the compounded Ca(...Continue Reading

References

Jan 15, 1977·The Biochemical Journal·G van de WerveH G Hers
Apr 1, 1992·The Journal of Cell Biology·W C WetselY A Hannun
Feb 1, 1992·British Journal of Pharmacology·S KeppensH De Wulf
Dec 1, 1991·The American Journal of Physiology·C E Bear, C H Li
Mar 1, 1990·The American Journal of Physiology·C E Bear
Apr 1, 1991·Trends in Pharmacological Sciences·S E O'ConnorP Leff
Aug 1, 1988·The Journal of General Physiology·R Horn, A Marty
Nov 1, 1987·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J L CruiseG Michalopoulos
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L B Ray, T W Sturgill
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Jan 1, 1983·The American Journal of Physiology·R Wondergem
Mar 15, 1981·The Biochemical Journal·J P DehayeJ H Exton
Mar 16, 1995·Biochimica Et Biophysica Acta·S M Keyse
May 1, 1994·Biochemical Society Transactions·L AgiusT H Thomas
Apr 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·S KeppensH De Wulf
Mar 11, 1999·Journal of Receptor and Signal Transduction Research·G G Yegutkin, G Burnstock
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·J W Putney

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Citations

Nov 26, 2013·Purinergic Signalling·Geoffrey BurnstockSimon C Robson
Feb 15, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Laszlo KölesPeter Illes
Mar 15, 2005·The Journal of Pharmacology and Experimental Therapeutics·C Jane DixonMichael R Boarder
Aug 19, 2005·American Journal of Physiology. Cell Physiology·Jung Sun HeoHo Jae Han

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