期刊
PLOS ONE
卷 11, 期 4, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0152446
关键词
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资金
- Basic Science Research Program through National Foundation of Korea - Ministry of Science, ICT & Future Planning [2013R1A1A1006655]
- Max Planck Society
- Korea Ministry of Education, Science and Technology, Gyeongsangbuk-Do and Pohang City
- [DK-020595]
- [DK-072473]
- [AG-042151]
- National Research Foundation of Korea [2013R1A1A1006655] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Pancreatic islets are functional units involved in glucose homeostasis. The multicellular system comprises three main cell types; beta and a cells reciprocally decrease and increase blood glucose by producing insulin and glucagon pulses, while the role of delta cells is less clear. Although their spatial organization and the paracrine/autocrine interactions between them have been extensively studied, the functional implications of the design principles are still lacking. In this study, we formulated a mathematical model that integrates the pulsatility of hormone secretion and the interactions and organization of islet cells and examined the effects of different cellular compositions and organizations in mouse and human islets. A common feature of both species was that islet cells produced synchronous hormone pulses under low-and high-glucose conditions, while they produced asynchronous hormone pulses under normal glucose conditions. However, the synchronous coordination of insulin and glucagon pulses at low glucose was more pronounced in human islets that had more a cells. When beta cells were selectively removed to mimic diabetic conditions, the anti-synchronicity of insulin and glucagon pulses was deteriorated at high glucose, but it could be partially recovered when the re-aggregation of remaining cells was considered. Finally, the third cell type, delta cells, which introduced additional complexity in the multicellular system, prevented the excessive synchronization of hormone pulses. Our computational study suggests that controllable synchronization is a design principle of pancreatic islets.
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