1. Academic Validation
  2. Long-term AICAR administration and exercise prevents diabetes in ZDF rats

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.
Rasmus Pold 1 Lasse S Jensen Niels Jessen Esben S Buhl Ole Schmitz Allan Flyvbjerg Nobuharu Fujii Laurie J Goodyear Carsten F Gotfredsen Christian L Brand Sten Lund
Affiliations

Affiliation

  • 1 Medical Research Laboratory and Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark.
Abstract

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.

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