Design principles of the paradoxical feedback between pancreatic alpha and beta cells

Abstract Mammalian glucose homeostasis is controlled by the antagonistic hormones insulin and glucagon, secreted by pancreatic beta and alpha cells respectively. These two cell types are adjacently located in the islets of Langerhans and affect each others’ secretions in a paradoxical manner: while...

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Autores principales:	Immacolata Garzilli, Shalev Itzkovitz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/842b91bfe3374bf2a79a625849f3eb22
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spelling	oai:doaj.org-article:842b91bfe3374bf2a79a625849f3eb222021-12-02T16:08:25ZDesign principles of the paradoxical feedback between pancreatic alpha and beta cells10.1038/s41598-018-29084-42045-2322https://doaj.org/article/842b91bfe3374bf2a79a625849f3eb222018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29084-4https://doaj.org/toc/2045-2322Abstract Mammalian glucose homeostasis is controlled by the antagonistic hormones insulin and glucagon, secreted by pancreatic beta and alpha cells respectively. These two cell types are adjacently located in the islets of Langerhans and affect each others’ secretions in a paradoxical manner: while insulin inhibits glucagon secretion from alpha cells, glucagon seems to stimulate insulin secretion from beta cells. Here we ask what are the design principles of this negative feedback loop. We systematically simulate the dynamics of all possible islet inter-cellular connectivity patterns and analyze different performance criteria. We find that the observed circuit dampens overshoots of blood glucose levels after reversion of glucose drops. This feature is related to the temporal delay in the rise of insulin concentrations in peripheral tissues, compared to the immediate hormone action on the liver. In addition, we find that the circuit facilitates coordinate secretion of both hormones in response to protein meals. Our study highlights the advantages of a paradoxical paracrine feedback loop in maintaining metabolic homeostasis.Immacolata GarzilliShalev ItzkovitzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Immacolata Garzilli Shalev Itzkovitz Design principles of the paradoxical feedback between pancreatic alpha and beta cells
description	Abstract Mammalian glucose homeostasis is controlled by the antagonistic hormones insulin and glucagon, secreted by pancreatic beta and alpha cells respectively. These two cell types are adjacently located in the islets of Langerhans and affect each others’ secretions in a paradoxical manner: while insulin inhibits glucagon secretion from alpha cells, glucagon seems to stimulate insulin secretion from beta cells. Here we ask what are the design principles of this negative feedback loop. We systematically simulate the dynamics of all possible islet inter-cellular connectivity patterns and analyze different performance criteria. We find that the observed circuit dampens overshoots of blood glucose levels after reversion of glucose drops. This feature is related to the temporal delay in the rise of insulin concentrations in peripheral tissues, compared to the immediate hormone action on the liver. In addition, we find that the circuit facilitates coordinate secretion of both hormones in response to protein meals. Our study highlights the advantages of a paradoxical paracrine feedback loop in maintaining metabolic homeostasis.
format	article
author	Immacolata Garzilli Shalev Itzkovitz
author_facet	Immacolata Garzilli Shalev Itzkovitz
author_sort	Immacolata Garzilli
title	Design principles of the paradoxical feedback between pancreatic alpha and beta cells
title_short	Design principles of the paradoxical feedback between pancreatic alpha and beta cells
title_full	Design principles of the paradoxical feedback between pancreatic alpha and beta cells
title_fullStr	Design principles of the paradoxical feedback between pancreatic alpha and beta cells
title_full_unstemmed	Design principles of the paradoxical feedback between pancreatic alpha and beta cells
title_sort	design principles of the paradoxical feedback between pancreatic alpha and beta cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/842b91bfe3374bf2a79a625849f3eb22
work_keys_str_mv	AT immacolatagarzilli designprinciplesoftheparadoxicalfeedbackbetweenpancreaticalphaandbetacells AT shalevitzkovitz designprinciplesoftheparadoxicalfeedbackbetweenpancreaticalphaandbetacells
_version_	1718384481590575104

Design principles of the paradoxical feedback between pancreatic alpha and beta cells

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