期刊
CELL SYSTEMS
卷 7, 期 1, 页码 118-+出版社
CELL PRESS
DOI: 10.1016/j.cels.2018.05.013
关键词
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资金
- PRESTO (Elucidation and Regulation in the Dynamic Maintenance and Transfiguration of Homeostasis in Living Body) from the Japan Science and Technology (JST)
- Japan Society for the Promotion of Science (JSPS) [16H06577]
- CREST (Creation of Fundamental Technologies for Understanding and Control of Biosystem Dynamics) from the JST [JPMJCR12W3]
- JSPS [17H06300, 17H06299]
Cells respond to various extracellular stimuli through a limited number of signaling pathways. One strategy to process such stimuli is to code the information into the temporal patterns of molecules. Although we showed that insulin selectively regulated molecules depending on its temporal patterns using Fao cells, the in vivo mechanism remains unknown. Here, we show how the insulin-AKT pathway processes the information encoded into the temporal patterns of blood insulin. We performed hyperinsulinemic-euglycemic clamp experiments and found that, in the liver, all temporal patterns of insulin are encoded into the insulin receptor, and downstream molecules selectively decode them through AKT. S6K selectively decodes the additional secretion information. G6Pase interprets the basal secretion information through FoxO1, while GSK3 beta decodes all secretion pattern information. Mathematical modeling revealed the mechanism via differences in network structures and from sensitivity and time constants. Given that almost all hormones exhibit distinct temporal patterns, temporal coding may be a general principle of system homeostasis by hormones.
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