A Novel Hexokinase, HKDC1, regulates glucose homeostasis during pregnancy

Gestational diabetes mellitus (GDM), diabetes during pregnancy, increases morbidity for both mother and child. Recent genome wide association studies (GWAS) exploring associations in GDM are beginning to reveal new genetic links. One of the stronger genetic findings is within the loci containing the gene for HKDC1 (hexokinase domain containing 1, unpublished data). While the biological role of this gene is unknown, sequence analyses suggest it is a putative hexokinase. While 4 hexokinases (HKs, designated I-IV) are traditional thought to exist, this gene encodes a hypothesized 5th hexokinase. Considering the important role of hexokinases in introducing glucose into all metabolic pathways, the first goal of this proposal is to determine whether the HKDC1 gene encodes a protein with hexokinase activity, where these studies will use isolated protein to investigate in great detail if HKDC1 acts similar to the other HKs. The second goal of this proposal is to determine the in vivo role of HKDC1 in the regulation of glucose homeostasis during pregnancy using genetic knockout models. Taken together, these studies are intended to reveal a novel gene, that has hexokinase activity and is involved in the regulation of glucose homeostasis during pregnancy.