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Leucine stimulates Sirt1 and AMPK signaling in vitro and in vivo. Since metformin converges on the same pathway, we have tested the ability of leucine to amplify the effects of metformin on AMPK-mediated hepatic lipid metabolism in diet-induced-obese insulin-resistant mice.Mice were fed high leucine (24g/kg diet) with or without sub-therapeutic levels of metformin (0.05–0.50g/kg diet) or therapeutic...
Background and objective: The Sirt1/AMPK signaling pathway is a key sensor of energy status and regulates glucose and lipid metabolism. Leucine (Leu) activates Sirt1 by lowering its Km for NAD + and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Since metformin (Met) converges on this pathway, we hypothesized that leucine would amplify its gluco-regulatory...
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