Atorvastatin induces insulin sensitization in Zucker lean and fatty rats.
BACKGROUND
The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors ('statins') have been implicated in preventing new onset type 2 diabetes, whereas the mechanism of this effect is not known. We investigated the effects of an HMG-CoA reductase inhibitor, atorvastatin, on insulin sensitization in Zucker lean and fatty rats.


RESULTS
In vivo studies of insulin sensitization were performed in chow fed Zucker lean and fatty rats treated with atorvastatin 50mg/kg/day (ATORVA_50) and results were compared to Zucker lean and fatty rats treated with drug vehicle only (CONT). Additional Zucker lean rats were treated with an intermediate dose of atorvastatin 25mg/kg/day (ATORVA_25). Treatment with atorvastatin resulted in a dose-dependent improvement in whole body insulin sensitivity in both lean and fatty rats, with an approximately two-fold increase in glucose infusion rate and glucose disposal (Rd) in ATORVA_50 versus CONT (p<0.01). Atorvastatin 50mg/kg/day resulted in an increase in 2-deoxyglucose (2-DOG) uptake by skeletal muscles (approximately two-fold increase in 2-DOG uptake in quadriceps (p=0.06) and gastrocnemius (p<0.01)) in lean Zucker rats. Insulin-stimulated phosphorylation of Akt/PKB was significantly increased in skeletal muscle of ATORVA_50 versus CONT in both lean and fatty rats.


CONCLUSIONS
Atorvastatin induces insulin sensitization in Zucker lean and fatty rats. This may be a clinically important pleiotropic effect if confirmed in insulin resistant humans.
Department of Medicine, Division of Endocrinology & Metabolism, University of Toronto, Ont., Canada; Department of Physiology, University of Toronto, Ont., Canada.
Victor
V
Wong
Laura
L
Stavar
Linda
L
Szeto
Kristine
K
Uffelman
Chao-Hung
CH
Wang
I George
IG
Fantus
Gary F
GF
Lewis
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D005500:Follow-Up Studies; D005947:Glucose / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D011758:Pyrroles; D000069059:Atorvastatin; D005947:Glucose