25: Insulin exerts an inhibitory effect on the contractility of human pregnant myometrium in vitro

Abstract

It has been demonstrated that human pregnant myometrium from women with Diabetes Mellitus (DM) displays poorer contractility than myometrium from non-diabetics. Since insulin has been shown to reduce the contractility of airway smooth muscle, we tested the hypothesis that the contractility of human myometrium from term pregnancy is reduced by insulin, and this may contribute to the debate on elevated cesarean delivery rates for dysfunctional labor in women with DM. Myometrial biopsies were obtained from women (n = 21) undergoing planned caesarean delivery at term, with informed consent and institutional approval. Myometrial strips were mounted for isometric recording in physiological salt solution (PSS) and stimulated by the addition of oxytocin (1 nM). Matched strips (2 or 3 per biopsy) were challenged with cumulative addition of vehicle or insulin, and the effects on contractility were measured and compared to controls. In the second series of experiments paired strips were treated with insulin (0.2 μM), or vehicle, for 15 min before oxytocin was added in cumulative increasing concentrations. Finally, the effect of a single concentration of insulin (0.2 μM) on spontaneous contractile activity was assessed. Insulin inhibited oxytocin induced contractions by 20 ± 8 % of those in vehicle-treated and time-matched controls with an IC50 of 0.13 μM (pIC50 = 6.8 ± 0.7, n = 5). Pre-treatment with insulin shifted the concentration-effect curve to oxytocin when compared to vehicle-treated controls, but the differences in curve parameters were not significant (paired t-test, P>0.05, n = 10). Insulin inhibited spontaneous contractions by 21 ± 7% (n = 6), in comparison to vehicle time-matched controls. Insulin exerts an inhibitory effect on human myometrial contractility in vitro. This effect of insulin may contribute to the poorer uterine contractility, and increased cesarean delivery rates, observed in pregnant women with Diabetes Mellitus.