Long-term AICAR administration and exercise prevents diabetes in ZDF rats

Diabetes. 2005 Apr;54(4):928-34. doi: 10.2337/diabetes.54.4.928.


Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / therapeutic use*
  • Animals
  • Blood Glucose
  • Diabetes Mellitus / enzymology*
  • Diabetes Mellitus / prevention & control*
  • Drug Administration Schedule
  • Enzyme Activation
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Male
  • Multienzyme Complexes / metabolism*
  • Muscle Fibers, Fast-Twitch / physiology
  • Myocardium / metabolism
  • Physical Exertion*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Subunits
  • Rats
  • Rats, Zucker
  • Ribonucleotides / therapeutic use*


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