AMP-activated protein kinase: Role in metabolism and therapeutic implications.
AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.
Schimmack
Greg
G
Texas Diabetes Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX 78207, USA.
Defronzo
Ralph A
RA
Musi
Nicolas
N
D055372:AMP-Activated Protein Kinases; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D015444:Exercise / Q000502:physiology; D006331:Heart Diseases / Q000201:enzymology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000502:physiology; D008099:Liver / Q000378:metabolism; D009097:Multienzyme Complexes / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases