HKDC1 Is a Novel Hexokinase Involved in Whole-Body Glucose Use
Autor: | William L. Lowe, Brian T. Layden, Anthony R. Angueira, Medha Priyadarshini, Timothy E. Reddy, Xianzhong Ding, Guang Yu Yang, Amy C. Y. Lo, Cong Guo, Korri S. Hershenhouse, Anton E. Ludvik, Carolina M. Pusec |
---|---|
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Genetically modified mouse medicine.medical_specialty medicine.medical_treatment Mice Transgenic Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Pregnancy Hexokinase Internal medicine medicine Animals Homeostasis Humans Glucose homeostasis Original Research Glucose tolerance test medicine.diagnostic_test Insulin Glucose Tolerance Test HKDC1 Glucose 030104 developmental biology chemistry In utero 030220 oncology & carcinogenesis Pregnancy Animal Female Blood sugar regulation Energy Metabolism |
Zdroj: | Endocrinology. 157:3452-3461 |
ISSN: | 1945-7170 0013-7227 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |