二甲双胍降糖作用的分子机制

二甲双胍降糖作用的分子机制

苏青

【期刊名称】《中华内分泌代谢杂志》

【年(卷),期】2016(032)009

【摘要】[Summary] Metformin mainly gives play to the hypoglycemic effect by reducing hepatic gluconeogenesis and activating glucose utilization of peripheral tissues. It is especially important that inhibiting hepatic gluconeogenesis in the hypoglycemic effect of metformin, of which molecular mechanisms are complicated and diverse, and are related to drug concentrations. Metformin, at pharmacologic concentrations, may directly inhibit mitochondria glycerophosphate dehydrogenase, resulting in reduced nicotinamide adenine dinucleotide ( NADH ) accumulation in cytosol and reducing pyruvate/lactate ratio, thus inhibiting gluconeogenesis. This effect is dependent on neither AMP nor adenosine monophosphate-activated protein kinase ( AMPK ) . Metformin at pharmacologic concentrations may also promote subunit assembly of AMPK to activate AMPK directly, thereby inhibiting hepatic gluconeogenesis. This effect is independent on AMP while dependent on AMPK. Metformin, at supra-pharmacologic concentrations, may inhibit mitochondrial complex Ⅰ, thus decrease ATP/AMP ratio, thereby activating AMPK and inhibiting hepatic gluconeogenesis. The reduction of ATP/AMP ratio also inhibits gluconeogenesis directly by energy