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
TPTF-induced
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 less than 0.02) for about 20 days. On the other hand, both plasma and adipose tissue
lipoprotein lipase (LPL) activity was markedly decreased (P less than 0.001) during this period, and
triglyceride production rates on day 2 after
TPTF administration was significantly decreased (P less than 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 less than 0.02). Inhibition of
glucagon release was also observed in the
arginine-loading test (P less than 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.