Strain differences in susceptibility to streptozotocin-induced diabetes: effects on hypertriglyceridemia and cardiomyopathy.

Abstract

Streptozotocin (STZ)-induced diabetes in Wistar rats results in severe hyperlipidemia and a characteristic cardiomyopathy. However, Wistar-Kyoto (WKY) rats made diabetic with a similar dose of STZ did not develop heart dysfunction or hypertriglyceridemia at 12 weeks post-STZ. We investigated whether an apparent resistance of the WKY strain to develop diabetic cardiomyopathy and hypertriglyceridemia following chronic diabetes could be due to a reduced susceptibility to the diabetogenic effects of STZ. Adult male WKY and Wistar rats were made diabetic with a moderate (55 mg/kg) or high (75 mg/kg) dose of STZ. At 6 weeks of diabetes, glucose tolerance, cardiac function, pancreatic insulin content and basal and post-heparin plasma lipolytic activity were determined. Administration of a moderate dose of STZ produced cardiac dysfunction in Wistar but not WKY rats at 6 weeks after diabetes induction. The same dose of STZ in WKY rats also resulted in a lesser degree of hyperglycemia and glucose intolerance, and significantly higher pancreatic insulin content relative to Wistar rats. Following a high dose of STZ, the apparent resistance to developing cardiomyopathy was lost in the WKY rats. As well, the WKY rats demonstrated an equal degree of hyperglycemia and glucose intolerance as Wistar rats. However, unlike the Wistar strain, WKY rats did not demonstrate either hypertriglyceridemia or a reduced heparin-releasable plasma lipoprotein lipase (LPL) activity following a high dose of STZ. These results suggest that the incidence of diabetes-related cardiomyopathy and hypertriglyceridemia in rats may be independently influenced by strain-dependent susceptibilities to the beta-cytotoxic effects of STZ. The absence of hypertriglyceridemia in severely diabetic WKY rats may be linked to the maintenance of a critical level of plasma LPL activity.