Metformin (1) is a widely-used antidiabetic ingredient for type 2 diabetes with no defined cellular mechanism of its action. Its efficacy has been considered to be due to the activation of AMP-activated protein kinase (AMPK) which is a major cellular regulator of lipid and glucose metabolism.
AMPK phosphorylates mouse acetyl-CoA carboxylase 1 (ACC1) at Ser79 and acetyl-CoA carboxylase 2 (ACC2) at Ser212, inactivating these enzymes. As the conversion of acetyl-CoA to malonyl-CoA by these enzymes is inhibited, subsequent lipid metabolism is regulated.
Therefore, Steinberg et al. generated mice with double-knock-in mutations in both ACC1 (Ser79Ala) and ACC2 (Ser212Ala) in order to investigate the mechanism of 1. As a result, they have reported that inhibitory phosphorylation of ACC1 and ACC2 by 1-activated AMPK is critical for controlling lipid metabolism, and the control may contribute to the improvement of insulin-resistance in obese mice.
Maximum quantity allowed is 999
Please select the quantity
