AMP-Activated Protein Kinase and Metabolic Control

Abstract

AMP-activated protein kinase (AMPK ), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile, and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction by acting on multiple cellular targets. In addition, it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs including the biguanides (metformin ) and thiazolidinedione s, as well as of insulin-sensitizing adipokines (e.g., adiponectin ). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes.