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Updated: Apr 17, 2026

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel
Cong Guo1, Anton E Ludvik2, Michelle E Arlotto3
11] Duke University Program in Genetics &Genomics, Durham, North Carolina 27708, USA [2] Center for Genomic &Computational Biology, Duke University School of Medicine, Durham, North Carolina 27708, USA.
Abstract:
Maternal glucose levels during pregnancy impact the developing fetus, affecting metabolic health both early and later on in life. Both genetic and environmental factors influence maternal metabolism, but little is known about the genetic mechanisms that alter glucose metabolism during pregnancy. Here, we report that haplotypes previously associated with gestational hyperglycaemia in the third trimester disrupt regulatory element activity and reduce expression of the nearby HKDC1 gene. We further find that experimentally reducing or increasing HKDC1 expression reduces or increases hexokinase activity, respectively, in multiple cellular models; in addition, purified HKDC1 protein has hexokinase activity in vitro. Together, these results suggest a novel mechanism of gestational glucose regulation in which the effects of genetic variants in multiple regulatory elements alter glucose homeostasis by coordinately reducing expression of the novel hexokinase HKDC1.
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