AMP-activated protein kinase and type 2 diabetes

Curr Med Chem. 2006;13(5):583-9. doi: 10.2174/092986706776055724.

Abstract

AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge, being activated in situations of high-energy phosphate depletion. Upon activation, AMPK functions to restore cellular ATP by modifying diverse metabolic pathways. AMPK is activated robustly by skeletal muscle contraction and myocardial ischemia, and may be involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and in decreased production of glucose, cholesterol, and triglycerides. Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinases
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / metabolism*
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • Structure-Activity Relationship

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Multienzyme Complexes
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases