Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.

ABSTRACT: Metformin is considered to be one of the most effective therapeutics for treating type 2 diabetes because it specifically reduces hepatic gluconeogenesis without increasing insulin secretion, inducing weight gain or posing a risk of hypoglycaemia. For over half a century, this agent has been prescribed to patients with type 2 diabetes worldwide, yet the underlying mechanism by which metformin inhibits hepatic gluconeogenesis remains unknown. Here we show that metformin non-competitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase, resulting in an altered hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and decreased hepatic gluconeogenesis. Acute and chronic low-dose metformin treatment effectively reduced endogenous gluc

SUBMITTER: Madiraju AK 

PROVIDER: S-EPMC4074244 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature