Long-term AICAR administration and exercise prevents diabetes in ZDF rats.
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.
Pold
Rasmus
R
Medical Research Laboratory and Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark.
Jensen
Lasse S
LS
Jessen
Niels
N
Buhl
Esben S
ES
Schmitz
Ole
O
Flyvbjerg
Allan
A
Fujii
Nobuharu
N
Goodyear
Laurie J
LJ
Gotfredsen
Carsten F
CF
Brand
Christian L
CL
Lund
Sten
S
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D001786:Blood Glucose; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D004789:Enzyme Activation; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D005082:Physical Exertion; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D011924:Rats, Zucker; D012265:Ribonucleotides / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D021122:Protein Subunits; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide