Rosiglitazone Treatment Enhances Acute AMP-Activated Protein Kinase–Mediated Muscle and Adipose Tissue Glucose Uptake in High-Fat–Fed Rats
- 1Diabetes and Obesity Research Program, Garvan Institute of Medical Research, University of New South Wales, Sydney, Australia
- 2St. Vincent’s Institute of Medical Research and the Department of Medicine, University of Melbourne, Victoria, Australia
- 3Commonwealth Scientific and Industrial Research Organization, Molecular Health Technologies, Victoria, Australia
- Address correspondence and reprint requests to Ji-Ming Ye, Diabetes and Obesity Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia. E-mail: j.ye{at}garvan.org.au
Abstract
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 AMPKα2 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.
- ACC, acetyl-CoA carboxylase
- AICAR, 5-aminoimidazole 4-carboxamide riboside
- AMPK, AMP-activated protein kinase
- GIR, glucose infusion rate
- HGO, hepatic glucose output
- LCACoA, long-chain fatty acyl-CoA
- pACC, phosphorylated ACC
- PPAR, peroxisome proliferator–activated receptor
- TZD, thiazolidinedione
Footnotes
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- Accepted July 18, 2006.
- Received October 10, 2005.
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