Abstract
The effect of long-term (4 months) insulin deficiency on triglyceride turnover was examined using Triton WR1339 in rats. Triglyceride secretion rate was estimated in rats 2 weeks and 4 months after induction of diabetes with 40 mg/kg of streptozotocin. By the second week diabetic rats showed prominent hyperglycemia and the plasma insulin level was very low. In spite of a lower triglyceride secretion rate compared to non-diabetic control rats, diabetic rats showed normotriglyceridemia. Thus, the estimated fractional catabolic rate for plasma triglyceride was decreased in the diabetic rats of 2 weeks duration. By the fourth month diabetic rats still showed a suppressed triglyceride secretion rate but plasma triglyceride was markedly higher than in the non-diabetic control rats. Therefore, their estimated fractional catabolic rate for plasma triglyceride was severely suppressed. They also showed hyperglycemia and hypercholesterolemia. The triglyceride-rich lipoprotein particles obtained after Triton injection in long-term diabetic rats were significantly cholesterol-enriched and triglyceride-depleted compared to control rats. These changes were already present in 2-week diabetic rats but the magnitude was significantly smaller that those in long-term diabetic rats. All of these abnormalities (including triglyceride turnover and the particle composition) were almost normalized by 2 weeks of insulin treatment (6 units/day). Thus, it was concluded from the present data that duration of insulin deficiency is an important determinant of triglyceride removal rate from the circulation in rats. Further modification of lipid composition of triglyceride-rich lipoprotein particles by long-term insulin-deficiency could be one of the reasons for this removal defect. Furthermore, overproduction of triglyceride cannot be a cause of hypertriglyceridemia seen in long-term uncontrolled experimental diabetes.
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