内科学
葡萄糖稳态
内分泌学
己糖激酶
生物
平衡
碳水化合物代谢
糖耐量受损
子宫内
糖耐量试验
怀孕
转基因小鼠
胎儿
能量稳态
胰岛素
转基因
糖尿病
2型糖尿病
新陈代谢
医学
胰岛素抵抗
糖酵解
肥胖
生物化学
遗传学
基因
作者
Anton E. Ludvik,Carolina M. Pusec,Medha Priyadarshini,Anthony R. Angueira,Cong Guo,Amy A. Lo,Korri S. Hershenhouse,Guang Yang,Xianzhong Ding,Timothy E. Reddy,William L. Lowe,Brian T. Layden
出处
期刊:Endocrinology
[The Endocrine Society]
日期:2016-07-20
卷期号:157 (9): 3452-3461
被引量:58
摘要
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.
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