Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action

Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of…

• G
  GlaxoSmithKline
• DK
  Deutsches Krebsforschungszentrum
• CM
  Cedars-Sinai Medical Center
• NI
  National Institutes of Health

  Awards: GM36780, DK26743, GM61390
• UO
  University of California, San Francisco
• NC
  National Center for Research Resources
• LC
  Liver Center, University of California, San Francisco

  Award: P30 DK26743