Myocardial lipoprotein lipase activity: regulation by diabetes and fructose-induced hypertriglyceridemia.
The decrease in myocardial lipoprotein lipase (LPL) activity observed previously in acute, severe models of insulin-deficient diabetes may be a compensatory response to hypertriglyceridemia and a sustained increase in fatty acid delivery to cardiomyocytes. The administration of fructose (10% solution in the drinking water for 4 days) to rats produced hypertriglyceridemia, but heparin-releasable LPL activity from perfused hearts and total and heparin-releasable LPL activities in isolated cardiomyocytes were not reduced. The acute (4 day) induction of a mild diabetic state (60 mg/kg streptozotocin) resulted in modest hypertriglyceridemia, and a selective decrease in heparin-releasable LPL activity in perfused hearts; LPL activity in cardiomyocytes from diabetic rat hearts was not reduced. Therefore, the diabetes-induced fall in myocardial LPL activity is not secondary to hypertriglyceridemia, since fructose treatment did not change LPL activity. Perfusion of rat hearts with 100 microM lysophosphatidylcholine (LPC) released a small amount of LPL activity into the perfusate, but only if albumin was omitted from the perfusion solution. Thus, the selective reduction in heparin-releasable LPL activity in perfused diabetic hearts is probably not the consequence of displacement by LPC, a lipolytic product of the LPL-catalyzed degradation of triacylglycerol-rich lipoproteins. Circulating LPL activity in the plasma of diabetic rats was not decreased relative to control plasma enzyme activity; therefore, the reduction in heparin-releasable LPL activity is not because circulating LPL was less available for uptake by the endothelium in diabetic hearts.
Liu
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Medical Research Council Signal Transduction Group, Faculty of Medicine, University of Calgary, Canada.
Severson
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DL
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005632:Fructose; D006493:Heparin / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000201:enzymology*; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008244:Lysophosphatidylcholines; D005632:Fructose; D006493:Heparin; D008071:Lipoprotein Lipase