Regulation of lipoprotein lipase activity in cardiac myocytes from control and diabetic rat hearts by plasma lipids.
The objective of this investigation was to test the hypothesis that the diabetes-induced reduction in lipoprotein lipase activity in cardiac myocytes may be due to hypertriglyceridemia. Administration of 4-aminopyrazolopyrimidine (50 mg/kg) to control rats for 24 h reduced plasma triacylglycerol levels and increased the heparin-induced release of lipoprotein lipase into the incubation medium of cardiac myocytes. The acute (3-5 days) induction of diabetes by streptozotocin (100 mg/kg) produced hypertriglyceridemia and reduced heparin-releasable lipoprotein lipase activity in cardiac myocytes. Treatment of diabetic rats with 4-aminopyrazolopyrimidine resulted in a fall in plasma triacylglycerol content and increased heparin-releasable lipoprotein lipase activity. Administration of Triton WR-1339 also resulted in hypertriglyceridemia, but the heparin-induced release of lipoprotein lipase from control cardiac myocytes was not reduced in the absence of lipolysis of triacylglycerol-rich lipoproteins. Treatment with Triton WR-1339 did, however, increase the heparin-induced release of lipoprotein lipase from diabetic cardiac myocytes. Preparation of cardiac myocytes with 0.9 mM oleic acid resulted in a decrease in both total cellular and heparin-releasable lipoprotein lipase activities. These results suggest that the diabetes-induced reduction in heart lipoprotein lipase activity may, at least in part, be due to an inhibitory effect of free fatty acids, derived either from lipoprotein degradation or from adipose tissue lipolysis, on lipoprotein lipase activity in (and (or) release from) cardiac myocytes.
Rodrigues
B
B
Medical Research Council of Canada Signal Transduction Group, Faculty of Medicine, University of Calgary, Alta.
Braun
J E
JE
Spooner
M
M
Severson
D L
DL
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D006493:Heparin / Q000494:pharmacology; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008055:Lipids; D009829:Oleic Acids; D014280:Triglycerides; C004420:4-aminopyrazolo(3,4-d)pyrimidine; D019301:Oleic Acid; D011092:Polyethylene Glycols; D006493:Heparin; D008071:Lipoprotein Lipase; D000225:Adenine; C016811:tyloxapol