AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.

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153

作者：

G.F. Merrill，E.J. Kurth，D.G. Hardie，W.W. Winder

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摘要：

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 microU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.

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关键词：

acetyl-CoA carboxylase malonyl-CoA palmitate oxidation 5-aminoimidazole-4-carboxamide riboside ZMP

DOI：

10.1046/j.1365-201X.1997.00251.x

被引量：

3218

年份：

1997