Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state

Metformin is widely used to treat hyperglycemia in individuals with type 2 diabetes. Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis. However, the molecular mechanism by which this pathway operates had remained elusive. Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained. Hepatocytes lacking AMPK displayed normal glucose production and gluconeogenic gene expression compared with wild-type hepatocytes. In contrast, gluconeogenesis was upregulated in LKB1-deficient hepatocytes.…

• UO
  University of Dundee
• DU
  Diabetes UK

  Award: 07/0003529
• EC
  European Commission

  Award: LSHM-CT-2004-005272
• SF
  Swedish Foundation for International Cooperation in Research and Higher Education
• AP
  Association pour la Recherche sur le Diabète
• MR
  Medical Research Council

  Award: 07/0003529