Archives for March 2011

Metformin: what cellular target?

Metformin, discovered in the 1920s appeared on the market in 1957. It belongs to one of the major families of products acting on insulin resistance in patients suffering from type 2 diabetes.

The target of its action is the mitochondrion1, more specifically complex 1, the entry point of NADH reduction which allows preservation of the proton gradient required for ATP production at the level of the mitochondrial membrane. However, the molecular target of metformin within complex 1 remains unknown.

Metformin is considered to have as a dominant cell action the activation of AMP kinase (AMPK) to which the inhibition of hepatic neoglucogenesis by metformin is attributed. Finally, metformin acts selectively on the liver; a transport protein from the Organic Cation Transporter (OCT), family,OCT1, being in control of the entry of metformin into hepatocytes.2,3

A work that has just been published in J Clin Invest4 questions the role of AMPK in the action of metformin on hepatic neoglucogenesis. Metformin continues to block hepatic glucose production.2 This is observed in the presence and absence of catalytic AMPK subunits in mouse hepatocyte primary cultures at concentrations comparable to those obtained under treatment in humans.