Time and dose selective glucose metabolism for glucose homeostasis and energy conversion in the liver
Hepatic glucose metabolism serves dual purposes: maintaining glucose homeostasis and converting glucose into energy sources; however, the underlying mechanisms are unclear. We quantitatively measured liver metabolites, gene expression, and phosphorylated insulin signaling molecules in mice orally administered varying doses of glucose, and constructed a transomic network. Rapid phosphorylation of insulin signaling molecules in response to glucose intake was observed, in contrast to the more gradual changes in gene expression. Glycolytic and gluconeogenic metabolites and expression of genes involved in glucose metabolism including glucose-6-phosphate, G6pc, and Pck1, demonstrated high glucose dose sensitivity. Whereas, glucokinase expression and glycogen accumulation showed low glucose dose sensitivity. During the early phase after glucose intake, metabolic flux was geared towards glucose homeostasis regardless of the glucose dose but shifted towards energy conversion during the late phase at higher glucose doses. Our research provides a comprehensive view of time- and dose-dependent selective glucose metabolism.
Authors
- Hiroshi Inoue (ORCID: https://orcid.org/0000-0002-7724-6637)
- Toshiya Kokaji (ORCID: https://orcid.org/0000-0002-1206-0532)
- Suguru Fujita (ORCID: https://orcid.org/0000-0001-7488-0045)
- Akira Terakawa
- Shinya Kuroda (ORCID: https://orcid.org/0000-0001-5059-8299)
- Hideki Maehara
- Tomoyoshi Soga (ORCID: https://orcid.org/0000-0001-9502-2509)
- Riku Egami
- Akiyoshi Hirayama (ORCID: https://orcid.org/0000-0002-0440-6820)
- Satoshi Ohno (ORCID: https://orcid.org/0000-0002-5642-8167)
- Atsushi J. Nagano (ORCID: https://orcid.org/0000-0001-7891-5049)
- Hikaru Sugimoto (ORCID: https://orcid.org/0000-0002-6468-0127)
- Y. Inaba (ORCID: https://orcid.org/0000-0001-9757-9669)
- Dongzi Li (ORCID: https://orcid.org/0000-0001-7931-0607)
- Keigo Morita (ORCID: https://orcid.org/0000-0001-8310-9607)
- Atsushi Hatano (ORCID: https://orcid.org/0000-0002-0386-5080)
- Saori Uematsu (ORCID: https://orcid.org/0000-0002-7033-9494)
- Yunfan Bai (ORCID: https://orcid.org/0000-0003-0479-2108)
- Yifei Pan
Institutions
- Kanazawa University (JP)
- Ryukoku University (JP)
- Tokyo Medical and Dental University (JP)
- Keio University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Niigata University (JP)
- The University of Tokyo (JP)
- Nara Institute of Science and Technology (JP)
Publication Details
- Journal
- npj Systems Biology and Applications
- Published
- 2024-09-30
- DOI
- https://doi.org/10.1038/s41540-024-00437-2
- Citations
- 3
- Primary Topic
- Diet and metabolism studies
- Type
- article
- Field-Weighted Citation Impact
- 0.98
Funders
- Takeda Science Foundation
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- Research Organization of Information and Systems
- Keio University
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- Japan Science and Technology Agency
- Institute of Genetics
- Core Research for Evolutional Science and Technology