Advances in the development of AMPK-activating compounds

Abstract

Background: AMP-activated protein kinase (AMPK) is an energy sensing enzyme that controls glucose and lipid metabolism. Objective: This review summarizes the present data on AMPK as a pharmacologic target for the treatment of metabolic disorders. Methods: The mechanisms governing AMPK activity and how this enzyme controls different metabolic pathways are reviewed briefly, and details about the effect that AMPK activators have on glucose metabolism are provided. Conclusion: Evidence obtained using the AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) suggests that AMPK promotes glucose transport into skeletal muscles and that this enzyme inhibits hepatic glucose production. AICAR also induces fatty acid oxidation in muscle and inhibits cholesterol synthesis in the liver. The metabolic effects of AICAR on glucose and lipid metabolism indicate that AMPK may be a good pharmacologic target for the treatment of type 2 diabetes and hypercholesterolemia. Novel AMPK-specific compounds are allowing researchers to examine whether this enzyme is a useful pharmacologic target for the treatment of human disease and whether chronic activation of AMPK will be safe.

Keywords::

• A-769662
• ACC
• AICAR
• AMPK
• metformin

Notes