Progestin Enhancement of the Plasma Insulin Response to Glucose in Rhesus Monkeys

Abstract

Treatment of Rhesus monkeys with pure progesterone for three weeks produced enhanced plasma insulin responses to intravenous glucose without altering glucose tolerance, and mild, but significant peripheral resistance to the hypoglycemic action of exogenous insulin. Several synthetic progestins currently employed in oral contraceptive agents also increased the plasma insulin responses to glucose. These changes were in marked contrast to the effect of acute administration of hydrocortisone, where there was a marked deterioration of glucose tolerance without any significant alteration in the plasma insulin response to glucose. From the data presented it appears that glucose tolerance remains normal following progesterone treatment because of a marked compensatory enhancement of the initial rate of release of insulin into the peripheral circulation following glucose stimulation. The mechanisms by which progestins produce these changes and the relative importance of progesterone in normal human pregnancy remains to be determined. Nevertheless, these data suggest that pure progesterone, like human placental lactogen, may be a diabetogenic factor in pregnancy and indicate that some, but not all, of the synthetic progestins may contribute to the changes in glucose and insulin metabolism observed in women taking oral contraceptive agents.