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While the results of this article do not exclude a direct action of metformin in the liver, they suggest that the first site of metformin action is the gut, via gut-hepatic crosstalk, and that it may play a role in the control of hepatic glucose production, integrating the site and mechanism of metformin action

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Both HIF-1 and HIF-2 have been shown to be associated with hepatic lipid metabolism, liver injury and the development of liver fibrosis [114, 115]

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