Streptozotocin-induced diabetes enhances cardiac heparin-releasable lipoprotein lipase activity in spontaneously hypertensive rats.
Vascular endothelial-bound lipoprotein lipase (LPL), also known as heparin-releasable LPL, catalyzes the breakdown of the triglyceride component of lipoproteins and is rate-limiting for free fatty acid transport to tissues. We previously demonstrated that heparin-releasable LPL activity increases in diabetic Wistar rat hearts, whereas with the development of hypertension in spontaneously hypertensive rats (SHR), there is a concomitant and progressive reduction in LPL activity. The objective of the present study was to examine the regulation of cardiac LPL activity in SHR-diabetic rats. Heparin perfusion of the isolated Langendorff heart induced the release of LPL activity. SHR hearts demonstrated a reduction in peak heparin-releasable LPL activity, relative to Wistar controls. However, induction of streptozotocin-induced diabetes in SHR, as in Wistar rats, increased peak heparin-releasable LPL activity in perfused hearts. The elevated heparin-releasable LPL peak could not be accounted for by enhanced LPL synthesis in that both cellular and surface-bound LPL activities in myocytes from SHR-diabetic rats were low relative to control. Chronic (12-day) insulin treatment of SHR-diabetic rats reduced the augmented heparin-releasable LPL activity and increased cell-associated LPL activity. Moreover, acute (90-minute) treatment of SHR-diabetic rats with rapid-acting insulin also reduced the heparin-releasable LPL activity to normal, although it had no effect on the low cellular LPL activity. These results demonstrate that the diabetes-induced augmentation of cardiac LPL counteracts the reduction in enzyme activity associated with hypertension. This may serve to increase the delivery of free fatty acid to the heart, and the resultant metabolic changes may lead to the severe cardiomyopathy observed in the hypertensive-diabetic rat heart.
Shepherd
G
G
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Cam
M C
MC
Sambandam
N
N
Abrahani
M A
MA
Rodrigues
B
B
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology*; D006493:Heparin / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D013311:Streptozocin
D007328:Insulin; D013311:Streptozocin; D006493:Heparin; D008071:Lipoprotein Lipase