Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1 alpha and promotes cell viability

R.E. Barry, B.B. Allan, E.P. Cummins, J.J. Kattla, A. Giblin, N. Scally, C.T. Taylor, Derek Brazil

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian cell growth and differentiation. Hypoxia arises when oxygen demand exceeds supply, and is a feature of multiple human diseases including stroke, cancer and renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and observed that insulin-induced cell viability is increased in hypoxia. We have characterized the role of protein kinase B (PKB/ Akt) in these cells as a potential mediator of this effect. PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia. Reduction of HIF1 alpha levels using antimycin-A or siRNA targeting HlF1 alpha did not affect PKB/Akt activation in hypoxia. Pharmacologic stabilization of HIF1 alpha independent of hypoxia did not increase insulin-stimulated PKB/Akt activation. Although increased insulin-stimulated cell viability was observed in hypoxia, no differences in the degree of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to growth factors such as insulin under adverse conditions such as hypoxia. alpha 2007 Elsevier GmbH. All rights reserved.
Original languageEnglish
Pages (from-to)393-403
Number of pages11
JournalEuropean Journal of Cell Biology
Volume86
Issue number7
DOIs
Publication statusPublished - 27 Jul 2007

ASJC Scopus subject areas

  • Cell Biology
  • Anatomy

Fingerprint

Dive into the research topics of 'Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1 alpha and promotes cell viability'. Together they form a unique fingerprint.

Cite this