Inhibition of glucose-induced insulin secretion by indomethacin and sodium salicylate in the fetal lamb.

The modulation of fetal insulin secretion by prostaglandins was studied with the aid of the prostaglandin synthesis inhibitors indomethacin and sodium salicylate in 10 chronically catheterized fetal lambs. Glucose-induced fetal insulin secretion was inhibited within 60 minutes by preinjection of either indomethacin or sodium salicylate in the fetal lambs. In the sodium salicylate experiments a significant (p less than 0.01) dose-related response (degree of insulin suppression) was noted between doses of 100 to 350 mg/kg of fetal weight. In a selected group of sodium salicylate injections prostaglandin levels were found to fall to 58% of control by 2 hours after injection. Five neonatal lambs exposed to a similar regimen were noted to have an exaggerated insulin response to glucose infusion when compared to fetal lambs. However, indomethacin or sodium salicylate pretreatment resulted in no suppression of glucose-induced insulin release. This finding may be of importance in explaining the observation of an increased incidence of fetal growth retardation after long-term exposure to salicylates in humans and in animal models.