AMP-kinase is the Main Target of Metformin in Regulating Type 2 Diabetes

AMP-activated protein kinase (AMPK) is a major cellular regulator that is activated when cellular energy levels are low and stimulates glucose uptake in skeletal muscle, fatty acid oxidation in adipose and other tissues, and decreases hepatic glucose production. The activation of AMPK's metabolic effects, particularly the metabolic shift from fat synthesis to fat oxidation and its ability to promote muscle glucose uptake, are expected to be beneficial in individuals with insulin resistance and/or type 2 diabetes. Since, AMPK is a central regulator of energy homeostasis, it has been considered to be an important therapeutic target for controlling human diseases including the metabolic syndrome. AMPK turns out to be the key target enzyme of metformin to reduce plasma glucose levels. Also, thiazolidinediones (TZDs) and 2-deoxyglucose have been shown to be indirect activators of AMPK. In this review, we discuss only the possible underlying mechanisms of metformin's miraculous strategies (in lowering plasma glucose level) at the molecular level, which will also provide an updated reference for the clinicians and researchers.