Selective Regulation of the Insulin-Akt Pathway by Simultaneous Processing of Blood Insulin Pattern in the Liver

研究成果: Chapter in Book/Report/Conference proceedingConference contribution

抄録

Insulin exhibits several temporal patterns, such as the 10- to 15-min pulsatile (minutes), additional (hours), and basal (days) secretions, leading to selective insulin responses in vivo; however, the mechanisms by which different temporal patterns of insulin selectively regulate downstream molecules remain unknown. Revealing the mechanisms of selective regulation by temporal patterns of insulin is pivotal for understanding insulin actions in vivo. We examined selective regulation of the insulin-Akt pathway and its mechanisms in the liver under hyperinsulinemic-euglycemic clamp conditions. We obtained time series data of the insulin-Akt pathway molecules using different stimulation patterns and developed a mathematical model that could reproduce these data. We found that all temporal patterns of the blood insulin levels are encoded into the insulin receptor (IR), and downstream molecules selectively and simultaneously decode them via protein kinase B (Akt or PKB). Mathematical modeling revealed the mechanisms via differences in network structures, sensitivity, and time constants. Moreover, we simulated the type II diabetes mellitus (T2DM) condition using the model and found that abnormal blood insulin patterns might contribute to the pathogenesis and/or progression of T2DM. Given that almost all hormones exhibit distinct temporal patterns, temporal coding may be a general principle of system homeostasis by hormones.

本文言語英語
ホスト出版物のタイトルMethods of Mathematical Oncology - Fusion of Mathematics and Biology
編集者Takashi Suzuki, Clair Poignard, Mark Chaplain, Vito Quaranta
出版社Springer
ページ203-213
ページ数11
ISBN(印刷版)9789811648656
DOI
出版ステータス出版済み - 2021
イベントInternational Symposium on Fusion of Mathematics and Biology, 2020 - Virtual, Online
継続期間: 10 26 202010 28 2020

出版物シリーズ

名前Springer Proceedings in Mathematics and Statistics
370
ISSN(印刷版)2194-1009
ISSN(電子版)2194-1017

会議

会議International Symposium on Fusion of Mathematics and Biology, 2020
CityVirtual, Online
Period10/26/2010/28/20

All Science Journal Classification (ASJC) codes

  • 数学 (全般)

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