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

P. R. Shepherd, B. T. Nave, J. Rincon, R. J. Haigh, E. Foulstone, C. Proud, J. R. Zierath, K. Siddle, H. Wallberg-Henriksson

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56 Citations (Scopus)

Abstract

Isolated skeletal muscle from healthy individuals was used to evaluate the role of phosphoinositide 3-kinase (PI 3-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 (≃ 1.7 fold), increased 3-o-methylglucose transport into human skeletal muscle strips (≃ 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 MAPkinase kinase (MEK) inhibitor PD 98059. However, PD98059 (up to 20 μmol/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 ≃ 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.

Original languageEnglish
Pages (from-to)1172-1177
Number of pages6
JournalDiabetologia
Volume40
Issue number10
DOIs
Publication statusPublished - 14 Oct 1997

Keywords

  • Glucose transport
  • Glycogen synthase
  • Human
  • Insulin
  • Map-kinase
  • Muscle
  • Phosphoinositide 3-kinase
  • Protein kinase B

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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