[Study on insulin resistance in rats treated with estrogen and progesterone--assessment with the euglycemic glucose...

To clarify the mechanism of insulin resistance in pregnancy, we have used the euglycemic glucose clamp technique in estradiol(E) treatment(n = 6), progesterone(P) treatment (n = 28), and Control(n = 29) female rats. E(10 micrograms/day) and P(10 mg/day) were injected subcutaneously into female rats for 14 days, to increase E and P concentrations to pregnant levels. Glucose production and glucose utilization were measured by using [3-3H]-glucose. The results were as follows, 1) Glucose production was almost suppressed at hyperinsulinemia(11,000 microU/ml) both Control and P treatment rats. Then at hyperinsulinemia, glucose utilization rate was almost equal to glucose infusion rate. 2) In P treatment rats glucose utilization was significantly lower (p less than 0.05) than in Control rats at hyperinsulinemia (11,000 microU/ml). 3) In P treatment rats glucose infusion rate was significantly lower than in Control rats at plasma insulin concentrations of 1,000 microU/ml(p less than 0.02), and 11,000 microU/ml(p less than 0.01), and lower than in E treatment rats at plasma insulin concentrations of 11,000 microU/ml(p less than 0.05). 4) In a dose-response curve for the effects of four different concentrations of insulin on glucose infusion rate, the insulin resistance induced by progesterone is characterized by a decreased responsiveness to insulin. The results suggest that progesterone may play an important role in inducing insulin resistance in pregnancy.