ESPE Abstracts

Gestational Diabetes (GDM) increases risk of developing type 2 diabetes in the mother and child later in life however, despite the increasing prevalence of GDM, its molecular mechanism remains unknown. A recent Genome-Wide Association Study (GWAS) identified a unique genetic association of the novel 5th hexokinase, hexokinase domain component-1 (HKDC1) to gestational glucose tolerance at 28 weeks of gestation linking it to GDM. We have previously shown that liver-specific overexpression of HKDC1 modulates maternal glucose tolerance, insulin sensitivity and nutrient mobilization during late gestation in pregnant mice. Since nutrient metabolism and mobilization is essential for offspring health, we hypothesized that maternal hepatic HKDC1 plays dictates offspring health. The aim of this study was to determine the role of hepatic HKDC1 on maternal and offspring glucose metabolism using our novel liver specific in utero HKDC1 knockout (HKDC1-LKO) mice to study glucose metabolism and nutrient mobilization at different gestational stages in offspring. Our results show that offspring born to HKDC1-LKO mice were lighter and had impaired glucose tolerance compared to offspring born to HKDC1 floxed mice (which served as controls) at 4 weeks. Further this difference seen at 4 weeks were lost at 21 weeks indicating that HKDC1 might be essential in the early development process. To assess this, we measured hepatic HKDC1 expression at different gestational ages and after birth and our exciting data shows that HKDC1 is highly expressed during gestation and shortly after birth. Taken together our data suggests that maternal hepatic HKDC1 expression plays important role in offspring development.