Involvement of phosphoinositide 3-kinase in insulin stimulation of MAP-kinase and phosphorylation of protein kinase-B in human skeletal muscle: implications for glucose metabolism

Shepherd, P.R. and Nave, B.T. and Rincon, J. and Haigh, R.J. and Foulstone, E.J. and Proud, Christopher G. and Zierath, J.R. and Siddle, K. and Wallberg-Henriksson, H. (1997) Involvement of phosphoinositide 3-kinase in insulin stimulation of MAP-kinase and phosphorylation of protein kinase-B in human skeletal muscle: implications for glucose metabolism. Diabetologia, 40 (10). pp. 1172-1177. ISSN 0012-186X. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1007/s001250050803

Abstract

Isolated skeletal muscle from healthy individuals was used to evaluate the role of phosphoinositide 3-kinase (PI3-kinase) in insulin signalling pathways regulating mitogen activated protein kinase (MAP-kinase) and protein kinase-B and to investigate whether MAP-kinase was involved in signalling pathways regulating glucose metabolism. Insulin stimulated glycogen synthase activity (approximate to 1.7 fold), increased 3-o-methylglucose transport into human skeletal muscle strips (approximate to 2 fold) and stimulated phosphorylation of the p42 ERK-2 isoform of MAP-kinase. This phosphorylation of p42 ERK2 was not blocked by the PI 3-kinase inhibitors LY294002 and wortmannin although it was blocked by the MAP-kinase kinase (MEK) inhibitor PD 95059. However, PD98059 (up to 20 mu mol/l) did not block insulin activation of glycogen synthase or stimulation of 3-o-methylglucose transport. Wortmannin and LY294002 did block insulin stimulation of protein kinase-B (PKB) phosphorylation and stimulation of 3-o-methylglucose transport was inhibited by wortmannin (IC50 approximate to 100 nmol/l). These results indicate that MAP-kinase is activated by insulin in human skeletal muscle by a PI 3-kinase independent pathway, Furthermore this activation is not necessary for insulin stimulation of glucose transport or activation of glycogen synthase in this tissue.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: T.J. Sango
Date Deposited: 13 May 2009 09:25
Last Modified: 23 Jun 2014 15:10
Resource URI: https://kar.kent.ac.uk/id/eprint/17948 (The current URI for this page, for reference purposes)
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