Peroxisome proliferator-activated receptor (PPAR) α or γ does not change ischemic tolerance in hearts from type 2 diabetic mice

Abstract

Recen: sludles have demonstrated that hearts from db/db mice (a model of type 2 diabetes) exhibit reduced contractile funchon and altered myocardlal metabolism (decreased glucose uliluation and Increased fatty acid oxidation) Furthermore, dbldb heark show a marked reduction in mechanical recovery fdlowmg global neflow ischemia, as compared to non-dlahelic dW+ mice In the presenl study we extined whether long-lerm beatmenl with two different peroxisome prdr veh&4raatad d&b mice were lncludad as controls. Plasma glucose concentrations ware r&cad k&wing PPARa (19 621 7 mM) and PPARy kabnents (22.04f1.3 mM). as compared to mntlol mica (44 6t2 1 mu) Myocardlal mat&&m, as measured after 13 min of global no-flow ischemia. was also markedly d~angad. Thus, PPARa and PPARy beatmants increased glucose oddation by l&fold and 1.7.fold, respeclively, while myocardlal palmitate oxidation was reduced by 34% and 37%. PPARn or PPAF+ treatment did not influence pre-lschemic ventricular function. Moreover, post. lschemlc recovery of cardiac o~lpul in hearts from PPARa-treated mice (56t12%) was not different from that in untreated conlrol mice (49+12%) ?ecovefy In hear& from PPARy-treated mace was relatively low (26i?%]. although not different from that in the corresponding untrealed controls (36?j%). Thus, both PPARa and PPARy treatments changed diabetes. Induced alterations in cardiac metabolism In dWdb diabettc mice. The altered melabolic profile did not, however. improve normoxic contractile fun&? or tolerance to Ischemia-reperfuson.