Triphenyltin Fluoride (TPTF) as a Diabetogenic Agent: TPTF Induces Diabetic Lipemia by Inhibiting Insulin Secretion from Morphologically Intact Rabbit B-Cell

Recent work in our laboratory has shown that oral administration of triphenyltin fluoride (TPTF) evokes hypertriglyceridemia in rabbits. The present experiments were conducted to elucidate the mechanism of TPTFinduced hypertriglyceridemia in rabbits by a combined biochemical and ultrastructural approach. After a single TPTF administration, fasting blood glucose and plasma triglyceride levels increased significantly (P < 0.02) for about 10 days. On the other hand, both plasma and adipose tissue lipoprotein lipase (LPL) activity was markedly decreased (P < 0.001) during this period, and triglyceride production rates on day 2 after TPTF administration were significantly decreased (P < 0.01). Density-gradient ultracentrifugation showed a remarkable accumulation of chylomicron and VLDL in the composition of plasma lipoproteins. Insulin injection to the hypertriglyceridemic rabbits induced a significant recovery of the decreased plasma LPL activity with a concomitant decrease of plasma triglyceride levels, while abeyance of insulin injection resulted in a decrease of LPL activity again. A significant inhibition of insulin release in response to the loading of glucose, glucagon, or arginine was observed in the TPTF rabbits (P < 0.02). Inhibition of glucagon release was also observed in the arginine-loading test (P < 0.01). Electron microscopic studies showed small abnormalities in the pancreatic islets of TPTF-treated rabbits. These findings suggest that TPTF inhibits insulin release from rabbit islets, subsequently inducing diabetic lipemia due to the insulin deficiency. Furthermore, it is possible to provide a new animal model for diabetes and diabetic lipemia by administration of TPTF to rabbits.