STRAIN DIFFERENCES IN SUSCEPTIBILITY TO STREPTOZOTOCIN-INDUCED DIABETES - EFFECTS ON HYPERTRIGLYCERIDEMIA AND CARDIOMYOPATHY

Objective: Streptozotocin (STZ)-induced diabetes in Wistar rats result s in severe hyperlipidemia and a characteristic cardiomyopathy. Howeve r, Wistar-Kyoto (WKY) rats made diabetic with a similar dose of STZ di d not develop heart dysfunction or hypertriglyceridemia at 12 weeks po st-STZ. We investigated whether an apparent resistance of the WKY stra in to develop diabetic cardiomyopathy and hypertriglyceridemia followi ng chronic diabetes could be due to a reduced susceptibility to the di abetogenic effects of STZ. Methods: Adult male WKY and Wistar rats wer e 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, panc reatic insulin content and basal and post-heparin plasma lipolytic act ivity were determined. Results: Administration of a moderate dose of S TZ produced cardiac dysfunction in Wistar but not WKY rats at 6 weeks after diabetes induction. The same dose of STZ in WKY rats also result ed in a lesser degree of hyperglycemia and glucose intolerance, and si gnificantly higher pancreatic insulin content relative to Wistar rats. Following a high dose of STZ, the apparent resistance to developing c ardiomyopathy was lost in the WKY rats. As well, the WKY rats demonstr ated an equal degree of hyperglycemia and glucose intolerance as Wista r rats. However, unlike the Wistar strain, WKY rats did not demonstrat e either hypertriglyceridemia or a reduced heparin-releasable plasma l ipoprotein lipase (LPL) activity following a high dose of STZ. Conclus ions: These results suggest that the incidence of diabetes-related car diomyopathy and hypertriglyceridemia in rats may be independently infl uenced by strain-dependent susceptibilities to the beta-cytotoxic effe cts of STZ. The absence of hypertriglyceridemia in severely diabetic W KY rats may be linked to the maintenance of a critical level of plasma LPL activity.