Effect of probucol on triglyceride turnover in streptozotocin-diabetic rats

The long-term effect of probucol on triglyceride turnover was examined in streptozotocin (40 mg/kg) diabetic rats. Two diabetic groups were prepared: one group received a probucol-containing (1%) diet (probucol-treated diabetic) and the other standard diet (diabetic control). After 4 months of probucol diet, triglyceride turnover was estimated using Triton WR1339. In diabetic control rats, glucose, triglyceride and cholesterol concentrations in plasma and in the very low density lipoprotein (VLDL) fraction were markedly elevated and plasma insulin was suppressed compared to non-diabetic control rats. There was no significant difference in body weight, plasma glucose and insulin between the 2 diabetic groups. However, the probucol-treated diabetic group showed significantly suppressed levels of triglyceride and cholesterol in total plasma and in the VLDL fraction compared to each corresponding diabetic control value. On the other hand, there were no significant differences in triglyceride secretion rate between the 2 diabetic groups. Newly secreted VLDL particles after Triton injection from diabetic control rats were significantly cholesterol-enriched and triglyceride-depleted compared to those from non-diabetic control rats. However, the composition of those from probucol-treated diabetic rats was similar to that of non-diabetic control group. Prominent hypertriglyceridemia without increase in triglyceride secretion rate in diabetic control group indicates triglyceride removal defect in diabetic rats. Significant suppression of plasma triglyceride level without changes in the triglyceride secretion rate in the probucol-treated diabetic group suggests that probucol stimulated triglyceride removal in diabetic rats. Thus, probucol might normalize VLDL composition, thereby contributing to accelerated triglyceride removal from the circulation of streptozotocin diabetic rats without affecting glucose metabolism.