Targeting the AMP-activated protein kinase for the treatment of type 2 diabetes.
The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated in response to conditions of cellular stress such as muscle contraction and hypoxia. In skeletal muscle, activation of AMPK leads to increased glucose uptake, enhanced insulin sensitivity and oxidation of fatty acids. In the liver, AMPK activation causes an increase in fatty acid oxidation and inhibition of glucose production. These effects on glucose and fat metabolism make AMPK an important pharmacological target for the treatment of type 2 diabetes. Studies done in animal models of type 2 diabetes have shown that pharmacological activation of AMPK with the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) decreases blood glucose and insulin concentrations. While strong efforts are underway in order to identify novel AMPK-activating compounds, the safety of chronic pharmacological activation of AMPK remains to be determined.
Musi
Nicolas
N
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Womens's Hospital, Harvard Medical School, Boston, MA, USA.
Goodyear
Laurie J
LJ
D055372:AMP-Activated Protein Kinases; D000273:Adipose Tissue / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D020536:Enzyme Activators / Q000494:pharmacology* / Q000627:therapeutic use; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism*; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012263:Ribonucleosides / Q000494:pharmacology / Q000627:therapeutic use
D020536:Enzyme Activators; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose