DIFFERENTIAL-EFFECTS OF STREPTOZOTOCIN-INDUCED DIABETES ON CARDIAC LIPOPROTEIN-LIPASE ACTIVITY

Lipoprotein lipase (LPL) is an endothelial-bound enzyme that is rate d etermining for the clearance of triacylglycerol-rich lipoproteins. Pre vious studies using rats with streptozotocin (STZ)-induced diabetes ha ve reported inconsistent effects on cardiac LPL activity or immunoreac tive protein. To examine the contribution of the severity and duration of diabetes on cellular and heparin-releasable cardiac LPL activity, Wistar rats were administered a high (100 mg/kg; D100) or moderate (55 mg/kg; D55) dose of STZ, and LPL activity was examined at various tim es after diabetes induction. Heparin perfusion of the isolated Langend orff control heart induced the release of LPL activity as an initial f ast phase followed by a slow phase of release. With increasing age, th e second phase of LPL release became more pronounced. Severe STZ-induc ed diabetes reduced heparin-releasable LPL activity by 1 week in the D 100 rats. However, in D55 rat hearts, peak heparin-releasable LPL acti vity was higher than that in control animals at 2 and 12 weeks after S TZ injection, with a complete absence of the delayed phase at 12 weeks . The elevated heparin-releasable LPL peak could not be explained by a n enhanced LPL synthesis because both cellular and surface-bound LPL a ctivities in myocytes from D55 rats were low, relative to control. Chr onic (12-day) insulin treatment of D55 rats prevented the rise in hepa rin-releasable LDL and the reduction in cell-associated LPL activity. Moreover, acute (90-min) treatment of D55 rats with rapid-acting insul in also reduced the heparin-releasable LPL activity to normal levels, although it had no effect on the low cellular LPL activity. When the h eparin-releasable LPL pool was allowed to recover for 1 h after remova l of the enzyme, D55 rat hearts continued to demonstrate a higher peak LPL activity after a second heparin perfusion. These studies demonstr ate that in moderate but not severe diabetes, there is an augmented pe ak heparin-releasable LPL activity. Whether or not this enhanced hepar in-releasable LPL activity has a pathological role in the diabetic hea rt has yet to be determined.