Protection by epicoprostanol against hyperglycemia and insulitis in normal and diabetic rats.

Epicoprostanol (3-alpha-hydroxy-5 beta-cholestanol) has been studied for its effects on blood glucose and plasma insulin levels in rodents. Epicoprostanol significantly induced hypoglycemia and increased insulin levels in rat blood plasma by 88% and 66% compared to that of control after 2 h and 4 h of acute treatment at 100 mg/kg dose. It also highly significantly lowered blood glucose levels in a dose dependent manner at 50, 100 and 200 mg/kg doses when administered to alloxan-rendered moderately diabetic rats after 120 and 240 min of treatment. Similarly, epicoprostanol, with the same dosage regimen, caused hypoglycemia in streptozotocin-induced severe diabetic rats, to a similar extent at the same time-points. However, the lowest dose (10 mg/kg) failed to produce a striking effect in either of the diabetic groups. In normoglycemic rats, plasma insulin levels were affected significantly after a single dose (100 mg/kg) of epicoprostanol. In contrast, diabetic animals suffering from insulitis showed a significant decline in hyperglycemia, strongly suggesting an insulin-like action of epicoprostanol. It seems likely that epicoprostanol acts through a mechanism other than hyperinsulinemia.