Progesterone and insulin-resistance in the pregnant rat. I. In vivo and in vitro studies.

The effects of pregnancy, progesterone treatment and of progesterone added in vitro on insulin-resistance have been assessed in rat adipocytes and hemidiaphragms. In progesterone treated female rats, the steroid antagonized in vivo the hypoglycemic effect of intravenously injected porcine insulin; the same results were obtained when the steroid was injected at the same time as insulin and there was no lag period between its appearance in the blood and its effect on blood glucose levels. Such a rapid effect differs from the generally accepted scheme for steroidal mode of action. The in vitro glucose uptake and oxidation by rat hemidiaphragms or adipocytes, whether or not stimulated by insulin, were decreased during pregnancy and after progesterone treatment of spayed females; the incorporation of [1-14 C]-glucose into glycogen of the diaphragm varied in the same way. However some of these effects were not decreased at 10 days of pregnancy, when progesterone levels only just began to rise. The effect of progesterone on insulin-resistance and glucose metabolism might occur at tissue level. The action of progesterone on adipocyte oxidation of glucose labeled at the C1 and the C6 position suggests that the steroid may act on the pentose cycle.