The deletion of Aryl-hydrocarbon Receptor Nuclear Translocator (ARNT) causes significant impaired glucose tolerance in pregnant mice. Our previous studies showed that metformin treatment of pregnant mice improved maternal glucose tolerance and also prevented offspring diabetes. Sulphonylureas have also been suggested as a possible treatment for GDM, but instead of decreasing fetal insulin (like metformin) they are likely to increase fetal insulin. We tested the effects of maternal treatment with Sulphonylurea (SU) on maternal glucose tolerance and offspring diabetes.

AIM: To investigate the effect of SU treatment on maternal and male offspring glucose tolerance

METHODS: β-ARNT females were time-mated with ARNT floxed control (AFC) males and AFC females with β-ARNT males, where half of the pregnant females were treated with SU. Glucose-tolerance tests (GTT) and Glucose-Stimulated Insulin Secretion (GSIS) were performed on day 16.5 of gestation. Litters had ~50% β-ARNT and ~50% AFC offspring and were observed for 20 weeks with metabolic testing including:-

Oxymax metabolic studies, measurement of food intake, GTT, GSIS, and Insulin Tolerance Testing (ITT)

RESULTS: The fasting glucose of pregnant β-ARNT females treated with SU was significantly lower than control group. They had improvement in glucose tolerance during pregnancy. Male offspring from females treated with SU had worse glucose tolerance compared to offspring from control mothers at fasting (p=0.06)) and 15 minutes (p=0.032) and were slightly heavier at 18 weeks (25.0±0.5 vs. 24.4±0.9, p=0.032). Statistical testing performed using Kolmogorov-Smirnov Test.

CONCLUSION: SU does improve maternal glucose tolerance, but in offspring of normal genotype worsens glucose tolerance and increases offspring weight.