• S Fediuc, M P Gaidhu, and R B Ceddia.
• Department of Kinesiology and Health Science, York University, 4700 Keele Street, Toronto, Ontario, Canada N3J 1P3.
• Endocrinology. 2006 Nov 1; 147 (11): 5170-7.

AbstractThe aim of this study was to investigate the effects of 5-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-induced AMP-activated protein kinase activation on glycogen metabolism in soleus (slow twitch, oxidative) and epitrochlearis (fast twitch, glycolytic) skeletal muscles. Isolated soleus and epitrochlearis muscles were incubated in the absence or presence of insulin (100 nM), AICAR (2 mM), and AICAR plus insulin. In soleus muscles exposed to insulin, glycogen synthesis and glycogen content increased 6.4- and 1.3-fold, respectively. AICAR treatment significantly suppressed ( approximately 60%) insulin-stimulated glycogen synthesis and completely prevented the increase in glycogen content induced by insulin. AICAR did not affect either basal or insulin-stimulated glucose uptake but significantly increased insulin-stimulated ( approximately 20%) lactate production in soleus muscles. Interestingly, basal glucose uptake was significantly increased ( approximately 1.4-fold) in the epitrochlearis muscle, even though neither basal nor insulin-stimulated rates of glycogen synthesis, glycogen content, and lactate production were affected by AICAR. We also report the novel evidence that AICAR markedly reduced insulin-induced Akt-Thr308 phosphorylation after 15 and 30 min exposure to insulin, which coincided with a marked reduction in glycogen synthase kinase 3 (GSK)-3alpha/beta phosphorylation. Importantly, phosphorylation of glycogen synthase was increased by AICAR treatment 45 min after insulin stimulation. Our results indicate that AICAR-induced AMP-activated protein kinase activation caused a time-dependent reduction in Akt308 phosphorylation, activation of glycogen synthase kinase-3alpha/beta, and the inactivation of glycogen synthase, which are compatible with the acute reduction in insulin-stimulated glycogen synthesis in oxidative but not glycolytic skeletal muscles.

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