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Publication
HKDC1 Is a Novel Hexokinase Involved in Whole-Body Glucose Use.
Authors Ludvik AE, Pusec CM, Priyadarshini M, Angueira AR, Guo C, Lo A, Hershenhouse KS,
Yang GY, Ding X, Reddy TE, Lowe WL, Layden BT
Submitted By Submitted Externally on 8/1/2018
Status Published
Journal Endocrinology
Year 2016
Date Published 9/1/2016
Volume : Pages 157 : 3452 - 61
PubMed Reference 27459389
Abstract In a recent genome-wide association study, hexokinase domain-containing protein
1, or HKDC1, was found to be associated with gestational glucose levels during
2-hour glucose tolerance tests at 28 weeks of pregnancy. Because our
understanding of the mediators of gestational glucose homeostasis is incomplete,
we have generated the first transgenic mouse model to begin to understand the
role of HKDC1 in whole-body glucose homeostasis. Interestingly, deletion of both
HKDC1 alleles results in in utero embryonic lethality. Thus, in this study, we
report the in vivo role of HKDC1 in whole-body glucose homeostasis using a
heterozygous-deleted HKDC1 mouse model (HKDC1(+/-)) as compared with matched
wild-type mice. First, we observed no weight, fasting or random glucose, or
fasting insulin abnormalities with aging in male and female HKDC1(+/-) mice.
However, during glucose tolerance tests, glucose levels were impaired in both
female and male HKDC1(+/-) mice at 15, 30, and 120 minutes at a later age (28 wk
of age). These glucose tolerance differences also existed in the female
HKDC1(+/-) mice at earlier ages but only during pregnancy. And finally, the
impaired glucose tolerance in HKDC1(+/-) mice was likely due to diminished
whole-body glucose use, as indicated by the decreased hepatic energy storage and
reduced peripheral tissue uptake of glucose in HKDC1(+/-) mice. Collectively,
these data highlight that HKDC1 is needed to maintain whole-body glucose
homeostasis during pregnancy but also with aging, possibly through its role in
glucose use.




Strains




Genes
SymbolDescription
Hkdc1hexokinase domain containing 1

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