AMP activated protein kinase: a next generation target for total metabolic control

Parimal Misra
Expert Opinion on Therapeutic Targets 2008, 12 (1): 91-100
Metabolic syndrome is characterized by a cluster of metabolic disorders, such as reduced glucose tolerance, hyperinsulinemia, hypertension, visceral obesity and lipid disorders. The benefit of exercise in maintaining total metabolic control is well known and recent research indicates that AMP-activated protein kinase (AMPK) may play an important role in exercise-related effects. AMPK is considered as a master switch in regulating glucose and lipid metabolism. AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high phosphate depletion. In the liver, activation of AMPK results in decreased production of plasma glucose, cholesterol, triglyceride and enhanced fatty acid oxidation. AMPK is also robustly activated by skeletal muscle contraction and myocardial ischemia, and is involved in the stimulation of glucose transport and fatty acid oxidation by these stimuli. In adipose tissue, activated AMPK inhibits deposition of fat, but enhances breakdown and burning of stored fat, resulting in reduction of body weight. The two leading diabetic drugs, namely metformin and rosiglitazone, and adipokines, such as adiponectin and leptin, show their metabolic effects partially through AMPK. These data suggest that AMPK may be a key player in the development of new treatments for obesity, Type 2 diabetes and the metabolic syndrome. In this review, the author provide insight into the role of AMPK as a probable target for treatment of metabolic syndrome.

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