Model for glucagon secretion by pancreatic α-cells.

Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved...

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Autores principales:	Virginia González-Vélez, Geneviève Dupont, Amparo Gil, Alejandro González, Iván Quesada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d1ee3fd67a14b8995fa79fdf091d0c9
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spelling	oai:doaj.org-article:5d1ee3fd67a14b8995fa79fdf091d0c92021-11-18T07:25:54ZModel for glucagon secretion by pancreatic α-cells.1932-620310.1371/journal.pone.0032282https://doaj.org/article/5d1ee3fd67a14b8995fa79fdf091d0c92012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22412861/?tool=EBIhttps://doaj.org/toc/1932-6203Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic Ca2+, as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet Ca2+ level. This observation is in line with previous work reporting that Ca2+ dynamics, mainly frequency, is altered by insulin. Thus, the present results emphasize the main role played by Ca2+ and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological conditions.Virginia González-VélezGeneviève DupontAmparo GilAlejandro GonzálezIván QuesadaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32282 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Virginia González-Vélez Geneviève Dupont Amparo Gil Alejandro González Iván Quesada Model for glucagon secretion by pancreatic α-cells.
description	Glucagon hormone is synthesized and released by pancreatic α-cells, one of the islet-cell types. This hormone, along with insulin, maintains blood glucose levels within the physiological range. Glucose stimulates glucagon release at low concentrations (hypoglycemia). However, the mechanisms involved in this secretion are still not completely clear. Here, using experimental calcium time series obtained in mouse pancreatic islets at low and high glucose conditions, we propose a glucagon secretion model for α-cells. Our model takes into account that the resupply of releasable granules is not only controlled by cytoplasmic Ca2+, as in other neuroendocrine and endocrine cells, but also by the level of extracellular glucose. We found that, although calcium oscillations are highly variable, the average secretion rates predicted by the model fall into the range of values reported in the literature, for both stimulated and non-stimulated conditions. For low glucose levels, the model predicts that there would be a well-controlled number of releasable granules refilled slowly from a large reserve pool, probably to ensure a secretion rate that could last for several minutes. Studying the α-cell response to the addition of insulin at low glucose, we observe that the presence of insulin reduces glucagon release by decreasing the islet Ca2+ level. This observation is in line with previous work reporting that Ca2+ dynamics, mainly frequency, is altered by insulin. Thus, the present results emphasize the main role played by Ca2+ and glucose in the control of glucagon secretion by α-cells. Our modeling approach also shows that calcium oscillations potentiate glucagon secretion as compared to constant levels of this cellular messenger. Altogether, the model sheds new light on the subcellular mechanisms involved in α-cell exocytosis, and provides a quantitative predictive tool for studying glucagon secretion modulators in physiological and pathological conditions.
format	article
author	Virginia González-Vélez Geneviève Dupont Amparo Gil Alejandro González Iván Quesada
author_facet	Virginia González-Vélez Geneviève Dupont Amparo Gil Alejandro González Iván Quesada
author_sort	Virginia González-Vélez
title	Model for glucagon secretion by pancreatic α-cells.
title_short	Model for glucagon secretion by pancreatic α-cells.
title_full	Model for glucagon secretion by pancreatic α-cells.
title_fullStr	Model for glucagon secretion by pancreatic α-cells.
title_full_unstemmed	Model for glucagon secretion by pancreatic α-cells.
title_sort	model for glucagon secretion by pancreatic α-cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/5d1ee3fd67a14b8995fa79fdf091d0c9
work_keys_str_mv	AT virginiagonzalezvelez modelforglucagonsecretionbypancreaticacells AT genevievedupont modelforglucagonsecretionbypancreaticacells AT amparogil modelforglucagonsecretionbypancreaticacells AT alejandrogonzalez modelforglucagonsecretionbypancreaticacells AT ivanquesada modelforglucagonsecretionbypancreaticacells
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Model for glucagon secretion by pancreatic α-cells.

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