Toggle Main Menu Toggle Search

Open Access padlockePrints

The role of protein kinase B/Akt in insulin-induced inactivation of phosphorylase in rat hepatocytes

Lookup NU author(s): Dr Susan Aiston, Dr Laura Hampson, Dr Catherine Arden, Professor Loranne Agius

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Aims/hypothesis: An insulin signalling pathway leading from activation of protein kinase B (PKB, also known as Akt) to phosphorylation (inactivation) of glycogen synthase kinase-3 (GSK-3) and activation of glycogen synthase is well characterised. However, in hepatocytes, inactivation of GSK-3 is not the main mechanism by which insulin stimulates glycogen synthesis. We therefore tested whether activation of PKB causes inactivation of glycogen phosphorylase. Materials and methods: We used a conditionally active form of PKB, produced using recombinant adenovirus, to test the role of acute PKB activation in the control of glycogen phosphorylase and glycogen synthesis in hepatocytes. Results: Conditional activation of PKB mimicked the inactivation of phosphorylase, the activation of glycogen synthase, and the stimulation of glycogen synthesis caused by insulin. In contrast, inhibition of GSK-3 caused activation of glycogen synthase but did not mimic the stimulation of glycogen synthesis by insulin. PKB activation and GSK-3 inhibition had additive effects on the activation of glycogen synthase, indicating convergent mechanisms downstream of PKB involving inactivation of either phosphorylase or GSK-3. Glycogen synthesis correlated inversely with the activity of phosphorylase-a, irrespective of whether this was modulated by insulin, by PKB activation or by a selective phosphorylase ligand, supporting an essential role for phosphorylase inactivation in the glycogenic action of insulin in hepatocytes. Conclusions/interpretation: In hepatocytes, the acute activation of PKB, but not the inhibition of GSK-3, mimics the stimulation of glycogen synthesis by insulin. This is explained by a pathway downstream of PKB leading to inactivation of phosphorylase, activation of glycogen synthase, and stimulation of glycogen synthesis, independent of the GSK-3 pathway. © Springer-Verlag 2005.


Publication metadata

Author(s): Aiston S, Hampson LJ, Arden C, Iynedjian PB, Agius L

Publication type: Article

Publication status: Published

Journal: Diabetologia

Year: 2006

Volume: 49

Issue: 1

Pages: 174-182

ISSN (print): 0012-186X

ISSN (electronic): 1432-0428

Publisher: Springer Berlin

URL: http://dx.doi.org/10.1007/s00125-005-0068-4

DOI: 10.1007/s00125-005-0068-4

PubMed id: 16341839


Altmetrics

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share