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AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats


Iglesias, MA and Ye, JM and Frangioudakis, G and Saha, AK and Tomas, E and Ruderman, NB and Cooney, J and Kraegen, EW, AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats, Diabetes, 51, (1) pp. 2886-2894. ISSN 0012-1797 (2002) [Refereed Article]

Copyright Statement

Copyright 2002 American Diabetes Association.

DOI: doi:10.2337/diabetes.51.10.2886


Exercise improves insulin sensitivity. As AMP-activated protein kinase (AMPK) plays an important role in muscle metabolism during exercise, we investigated the effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) on insulin action in insulin-resistant high-fat-fed (HF) rats. Rats received a subcutaneous injection of 250 mg/kg AICAR (HF-AIC) or saline (HF-Con). The next day, euglycemic-hyperinsulinemic clamp studies were performed. Glucose infusion rate during the clamp was enhanced (50%) in HF-AIC compared with HF-Con rats. Insulin-stimulated glucose uptake was improved in white but not in red quadriceps, whereas glycogen synthesis was improved in both red and white quadriceps of HF-AIC rats. HF-AIC rats also showed increased insulin suppressibility of hepatic glucose output (HGO). AICAR-induced responses in both liver and muscle were accompanied by reduced malonyl-CoA content. Clamp HGO correlated closely with hepatic triglyceride content (r = 0.67, P < 0.01). Thus, a single dose of AICAR leads to an apparent enhancement in whole-body, muscle, and liver insulin action in HF rats that extends beyond the expected time of AMPK activation. Whether altered tissue lipid metabolism mediates AICAR effects on insulin action remains to be determined. Follow-up studies suggest that at least some of the post-AICAR insulin-enhancing effects also occur in normal rats. Independent of this, the results suggest that pharmacological activation of AMPK may have potential in treating insulin-resistant states and type 2 diabetes.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biochemistry and metabolomics
Research Field:Metabolic medicine
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Iglesias, MA (Dr Miguel Iglesias)
ID Code:80263
Year Published:2002
Web of Science® Times Cited:238
Deposited By:Health Sciences A
Deposited On:2012-10-25
Last Modified:2013-03-21

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