Load-induced changes in vivo alter substrate fluxes and insulin responsiveness of rat heart in vitro.
It has been observed that opposite changes in cardiac workload result in similar changes in cardiac gene expression. In the current study, the hypothesis that altered gene expression in vivo results in altered substrate fluxes in vitro was tested. Hearts were perfused for 60 minutes with Krebs-Henseleit buffer containing glucose (5 mmol/L) and oleate (0.4 mmol/L). At 30 minutes, either insulin (1 mU/mL) or epinephrine (1 micromol/L) was added. Hearts weighed 35% less after unloading and 25% more after aortic banding. Contractile function in vitro was decreased in transplanted and unchanged in banded hearts. Epinephrine, but not insulin, increased cardiac power. Basal glucose oxidation was initially decreased and then increased by aortic banding. The stimulatory effects of insulin or epinephrine on glucose oxidation were reduced or abolished by unloading, and transiently reduced by banding. Oleate oxidation correlated with cardiac power both before and after stimulation with epinephrine, whereas glucose oxidation correlated only after stimulation. Malonyl-coenzyme A levels did not correlate with rates of fatty acid oxidation. Pyruvate dehydrogenase was not affected by banding or unloading. It was concluded that atrophy and hypertrophy both decrease insulin responsiveness and shift myocardial substrate preference to glucose, consistent with a shift to a fetal pattern of energy consumption; and that the isoform-specific changes that develop in vivo do not change the regulation of key metabolic enzymes when assayed in vitro.
Doenst
T
T
Division of Cardiology, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Goodwin
G W
GW
Cedars
A M
AM
Wang
M
M
Stepkowski
S
S
Taegtmeyer
H
H
D000818:Animals; D001284:Atrophy / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000503:physiopathology*; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D016027:Heart Transplantation; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D010477:Perfusion; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF
D005227:Fatty Acids; D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D019301:Oleic Acid; D008316:Malonyl Coenzyme A; D006003:Glycogen; D005947:Glucose; D004837:Epinephrine