Methyl palmoxirate increases Ca2+-myosin ATPase activity and changes myosin isoenzyme distribution in the diabetic rat heart.
Previous studies have shown that in rats diabetes mellitus leads to a decrease in cardiac ventricle myosin V1 and an increase in myosin V3 levels. Insulin administration reverts myosin isoenzyme distribution to normal levels. It is currently unclear whether the effects of insulin on myosin isoenzyme distribution are a direct effect of the hormone or are mediated through insulin-induced alterations in cardiac metabolism. To gain further insight into this question diabetic rats received methyl palmoxirate, a potent inhibitor of long-chain fatty acid oxidation. Administration of 25 mg methyl palmoxirate X kg body wt-1 X day-1 to diabetic rats for 4 wk leads to a partial reversal of the effects of diabetes. Myosin V1 predominance is re-established and Ca2+-activated myosin ATPase activity increases by 60% (Ca2+-myosin ATPase normal rats 1.067 +/- 0.13 mumol Pi X mg protein-1 X min-1, diabetic rats 0.609 +/- 0.05 mumol Pi X mg protein-1 X min-1, diabetic + methyl palmoxirate rats 0.912 +/- 0.06 mumol Pi X mg protein-1 X min-1). The methyl palmoxirate-induced increase in myosin V1 levels and Ca2+-activated myosin ATPase activity occurred in the absence of changes in insulin and thyroid hormone levels. Methyl palmoxirate may have acted through its known inhibitory effect on cardiac beta-oxidation and/or the resultant stimulatory effect on glycolytic flux. Our findings may indicate that changes in cardiac substrate consumption can influence myosin isoenzyme predominance.
Dillmann
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D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009218:Myosins / Q000378:metabolism*; D009929:Organ Size; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D007328:Insulin; D007527:Isoenzymes; D011422:Propionates; D000251:Adenosine Triphosphatases; D009218:Myosins; C017522:methyl 2-tetradecylglycidate; D002118:Calcium