AMP-activated protein kinase and muscle glucose uptake

Acta Physiol Scand. 2003 Aug;178(4):337-45. doi: 10.1046/j.1365-201X.2003.01168.x.


The AMP-activated protein kinase (AMPK) is an enzyme that is activated in situations where there are changes in the cellular energy status such as muscle contraction and hypoxia. AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin. Several studies support the hypothesis that AMPK plays an important role in the stimulation of muscle glucose uptake by these physiological and pharmacological stimuli. In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism. Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake. Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity. The activation of AMPK and associated increases in muscle glucose uptake are affected by factors such as glycogen content, exercise training and fibre type. The effects of AMPK on muscle glucose uptake makes this protein a promising pharmacological target for the treatment of type 2 diabetes.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / metabolism
  • Animals
  • Exercise / physiology
  • Glucose / metabolism*
  • Glycogen / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Metformin / pharmacology
  • Multienzyme Complexes / metabolism*
  • Muscle Contraction / physiology
  • Muscle Fibers, Skeletal / physiology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Nutritional Status / physiology
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Ribonucleotides / metabolism


  • Hypoglycemic Agents
  • Insulin
  • Multienzyme Complexes
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Glycogen
  • Metformin
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Glucose