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Rosiglitazone treatment enhances acute AMP-activated protein kinase-mediated muscle and adipose tissue glucose uptake in high-fat-fed rats


AMP-activated protein kinase (AMPK) has been implicated in the insulin-sensitizing actions of thiazolidinediones (TZDs), but it is not known whether TZD treatment can enhance tissue glucose uptake in response to AMPK activation. The present study investigated the influence of the TZD rosiglitazone on glucose turnover induced by intravenous infusion of the AMPK activator 5-aminoimidazole 4-carboxamide riboside (AICAR) under euglycemic and iso-insulinemic conditions in insulin-resistant high-fat-fed rats. We found that rosiglitazone treatment significantly enhanced AICAR-stimulated whole-body glucose disposal by 27% in high-fat-fed rats, and a 44% greater glucose infusion rate (both P < 0.01 vs. vehicle control rats) was required to maintain euglycemia. Along with this, both AICAR-stimulated glucose uptake and glucose incorporation into glycogen in muscle and adipose tissue were enhanced (P < 0.05). The enhanced glucose uptake and glycogen synthesis in muscle were associated with increased activity of total AMPK and the AMPKalpha2 subunit. In comparison, these effects were not apparent in rats fed standard rodent diet. Thus, our findings suggest that in addition to ameliorating insulin resistance, TZDs may enhance AMPK-stimulated glucose clearance into peripheral tissues in insulin-resistant states.

Type Journal
ISBN 0012-1797 (Print)
Authors Ye, J. M.;Dzamko, N.;Hoy, A. J.;Iglesias, M. A.;Kemp, B.;Kraegen, E. :
Responsible Garvan Author Prof Edward Kraegen
Publisher Name DIABETES
Published Date 2006-01-01
Published Volume 55
Published Issue 10
Published Pages 2797-804
Status Published in-print
URL link to publisher's version