Insulin receptor binding and tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes

OBJECTIVE: To ascertain whether the decreased glucose tolerance and insulin resistance found in normal and gestational diabetic pregnancy might be associated with changes in insulin receptor function.

METHODS: Eight nonpregnant healthy women (nonpregnant controls), eight healthy pregnant women (pregnant controls), and eight women with gestational diabetes were investigated. All were non-obese. Muscle biopsies were obtained from the vastus lateralis muscle, and insulin binding and tyrosine kinase activities in partially purified skeletal muscle insulin receptors were studied. The pregnant controls were investigated in late pregnancy, and the women with gestational diabetes were investigated at the time of diagnosis of gestational diabetes. A further examination was carried out 2 months after delivery.

RESULTS: Insulin binding at tracer insulin concentration (60 pmol/L) was diminished in women with gestational diabetes compared to nonpregnant controls (P < .05), whereas normal pregnant women did not differ from the other two groups. Postpartum, no differences in insulin binding were found between the groups. Basal and maximal tyrosine kinase activities toward the exogenous substrate poly(Glu4Tyr1) were the same in nonpregnant controls, pregnant controls, and women with gestational diabetes. Postpartum, no differences in tyrosine kinase activity were found among the groups. Moreover, no significant differences in insulin binding or tyrosine kinase activity were found comparing pregnancy and postpartum values within the groups.

CONCLUSION: The insulin resistance found in normal and gestational diabetic pregnancy is not likely to be caused by a defective insulin receptor tyrosine kinase, whereas decreased insulin receptor binding might have some pathogenic importance in gestational diabetes.