The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics

The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics

Abstract Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of $$\beta $$ β -cell mass and alteration of $$\beta $$ β -cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in $$\beta...

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Autores principales: Maryam Saadati, Yousef Jamali
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/f2c53237365148c787b151a405366822
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spelling oai:doaj.org-article:f2c53237365148c787b151a4053668222021-12-02T15:55:13ZThe effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics10.1038/s41598-021-89333-x2045-2322https://doaj.org/article/f2c53237365148c787b151a4053668222021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89333-xhttps://doaj.org/toc/2045-2322Abstract Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of $$\beta $$ β -cell mass and alteration of $$\beta $$ β -cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in $$\beta $$ β -cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of $$\beta $$ β -cell mass to $$\beta $$ β -cell function in T2D, we make use of a comprehensive electrophysiological model of human $$\beta $$ β -cell clusters. We find that defect in $$\beta $$ β -cell mass causes a functional decline in single $$\beta $$ β -cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular $${\text {Ca}}^{2+}$$ Ca 2 + concentration, which can lead to changes in insulin secretion dynamics and in insulin levels. The model demonstrates a good correspondence between suppression of synchronizing electrical activity and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both $$\beta $$ β -cell synchronization and metabolic coupling in the behavior of $${\text {Ca}}^{2+}$$ Ca 2 + concentration dynamics within human islets. Our results indicate that inter- $$\beta $$ β -cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the whole-cell conductance of delayed rectifier $$\text {K}^{+}$$ K + channels modifies oscillatory activity patterns of $$\beta $$ β -cell population lacking intercellular coupling, which significantly affect $${\text {Ca}}^{2+}$$ Ca 2 + concentration and insulin secretion.Maryam SaadatiYousef JamaliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Maryam Saadati
Yousef Jamali
The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
description Abstract Type 2 diabetes (T2D) is a challenging metabolic disorder characterized by a substantial loss of $$\beta $$ β -cell mass and alteration of $$\beta $$ β -cell function in the islets of Langerhans, disrupting insulin secretion and glucose homeostasis. The mechanisms for deficiency in $$\beta $$ β -cell mass and function during the hyperglycemia development and T2D pathogenesis are complex. To study the relative contribution of $$\beta $$ β -cell mass to $$\beta $$ β -cell function in T2D, we make use of a comprehensive electrophysiological model of human $$\beta $$ β -cell clusters. We find that defect in $$\beta $$ β -cell mass causes a functional decline in single $$\beta $$ β -cell, impairment in intra-islet synchrony, and changes in the form of oscillatory patterns of membrane potential and intracellular $${\text {Ca}}^{2+}$$ Ca 2 + concentration, which can lead to changes in insulin secretion dynamics and in insulin levels. The model demonstrates a good correspondence between suppression of synchronizing electrical activity and published experimental measurements. We then compare the role of gap junction-mediated electrical coupling with both $$\beta $$ β -cell synchronization and metabolic coupling in the behavior of $${\text {Ca}}^{2+}$$ Ca 2 + concentration dynamics within human islets. Our results indicate that inter- $$\beta $$ β -cellular electrical coupling depicts a more important factor in shaping the physiological regulation of islet function and in human T2D. We further predict that varying the whole-cell conductance of delayed rectifier $$\text {K}^{+}$$ K + channels modifies oscillatory activity patterns of $$\beta $$ β -cell population lacking intercellular coupling, which significantly affect $${\text {Ca}}^{2+}$$ Ca 2 + concentration and insulin secretion.
format article
author Maryam Saadati
Yousef Jamali
author_facet Maryam Saadati
Yousef Jamali
author_sort Maryam Saadati
title The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
title_short The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
title_full The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
title_fullStr The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
title_full_unstemmed The effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {Ca}}^{2+}$$ Ca 2 + dynamics
title_sort effects of beta-cell mass and function, intercellular coupling, and islet synchrony on $${\text {ca}}^{2+}$$ ca 2 + dynamics
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/f2c53237365148c787b151a405366822
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AT maryamsaadati effectsofbetacellmassandfunctionintercellularcouplingandisletsynchronyontextca2ca2dynamics
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