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Role of Gestational Hormones in the Induction of Insulin Resistance^*

EDMOND A. RYAN and LOUISE ENNS

Department of Medicine, University of Alberta Edmonton, Alberta, Canada T6G 2G3

Address all correspondence and requests for reprints to: Edmond A. Ryan, M.D., 7–117 Clinical Sciences Building, University of Alberta, Edmonton, Alberta, Canada T6G 2G3.

Pregnancy is associated with insulin resistance. We studied insulin binding and postbinding function in isolated adipocytes from pregnant and nonpregnant rats. We also used a primary culture system for female virgin rat adipocytes to assess the effects of gestational hormones in vitro on insulin binding and postbinding function. Insulin binding to adipocytes was normal during pregnancy, but [¹⁴C]3-O-methylglucose transport was reduced. When hCG or estradiol was added to the culture medium, no change in maximum [¹⁴C]3-O-methylglucose transport was found; however, maximum insulin binding was increased with estradiol. Progesterone and cortisol both decreased maximum insulin binding and [¹⁴C]3-O-methylglucose transport. PRL and placental lactogen decreased maximum [¹⁴C]3-0-methylglucose transport, but did not change insulin binding. When these hormones were added concurrently no change in insulin binding was found, but maximum [¹⁴C]3-O-methylglucose transport was reduced. We conclude that the insulin resistance of pregnancy is associated with a postbinding defect in insulin action. Estradiol increased insulin receptor binding, but during pregnancy this effect may be offset by the reduction in insulin binding induced by progesterone and cortisol. The postbinding defect in insulin action during pregnancy is probably related to increasing amounts of progesterone, cortisol, PRL, and placental lactogen.

^* This work was supported by an establishment grant from the Alberta Heritage Foundation for Medical Research. Presented in preliminary form at the Annual Meeting of the American Diabetes Association, Indianapolis, IN, 1987, and the Julia McFarlane Diabetes Research Unit Symposium on Insulin Action and Diabetes, Calgary, Alberta, Canada, 1987.

Clinical Investigator, Alberta Heritage Foundation for Medical Research.

Received December 28, 1987.

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