The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets
<p>Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca<sup>2+</sup> on intrinsic &al...
Main Authors: | , , , , , , |
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Format: | Journal article |
Language: | English |
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Cell Press
2024
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author | Acreman, S Ma, J Denwood, G Gao, R Tarasov, A Rorsman, P Zhang, Q |
author_facet | Acreman, S Ma, J Denwood, G Gao, R Tarasov, A Rorsman, P Zhang, Q |
author_sort | Acreman, S |
collection | OXFORD |
description | <p>Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca<sup>2+</sup> on intrinsic α-cell glucagon secretion. Blocking isradipine-sensitive L-type voltage-gated Ca<sup>2+</sup> (Ca<sub>v</sub>) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca<sup>2+</sup> oscillations or low-glucose-stimulated glucagon secretion. In contrast, depleting ER Ca<sup>2+</sup> with cyclopiazonic acid or blocking ER Ca<sup>2+</sup>-releasing ryanodine receptors abolished α-cell glucose sensitivity and low-glucose-stimulated glucagon secretion. ER Ca<sup>2+</sup> mobilization in α-cells is regulated by intracellular ATP and likely to be coupled to Ca<sup>2+</sup> influx through P/Q-type Ca<sub>v</sub> channels. ω-Agatoxin IVA blocked α-cell ER Ca<sup>2+</sup> release and cell exocytosis, but had no additive effect on glucagon secretion when combined with ryanodine. We conclude that glucose regulates glucagon secretion through the control of ER Ca<sup>2+</sup> mobilization, a mechanism that can be independent of α-cell electrical activity.</p> |
first_indexed | 2024-09-25T04:07:58Z |
format | Journal article |
id | oxford-uuid:d7566cb3-3da5-415c-97d2-880f5dfee844 |
institution | University of Oxford |
language | English |
last_indexed | 2024-09-25T04:07:58Z |
publishDate | 2024 |
publisher | Cell Press |
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spelling | oxford-uuid:d7566cb3-3da5-415c-97d2-880f5dfee8442024-05-31T15:32:35ZThe endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse isletsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d7566cb3-3da5-415c-97d2-880f5dfee844EnglishSymplectic ElementsCell Press2024Acreman, SMa, JDenwood, GGao, RTarasov, ARorsman, PZhang, Q<p>Glucagon is secreted by pancreatic α-cells to counteract hypoglycaemia. How glucose regulates glucagon secretion remains unclear. Here, using mouse islets, we studied the role of transmembrane and endoplasmic reticulum (ER) Ca<sup>2+</sup> on intrinsic α-cell glucagon secretion. Blocking isradipine-sensitive L-type voltage-gated Ca<sup>2+</sup> (Ca<sub>v</sub>) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca<sup>2+</sup> oscillations or low-glucose-stimulated glucagon secretion. In contrast, depleting ER Ca<sup>2+</sup> with cyclopiazonic acid or blocking ER Ca<sup>2+</sup>-releasing ryanodine receptors abolished α-cell glucose sensitivity and low-glucose-stimulated glucagon secretion. ER Ca<sup>2+</sup> mobilization in α-cells is regulated by intracellular ATP and likely to be coupled to Ca<sup>2+</sup> influx through P/Q-type Ca<sub>v</sub> channels. ω-Agatoxin IVA blocked α-cell ER Ca<sup>2+</sup> release and cell exocytosis, but had no additive effect on glucagon secretion when combined with ryanodine. We conclude that glucose regulates glucagon secretion through the control of ER Ca<sup>2+</sup> mobilization, a mechanism that can be independent of α-cell electrical activity.</p> |
spellingShingle | Acreman, S Ma, J Denwood, G Gao, R Tarasov, A Rorsman, P Zhang, Q The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title_full | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title_fullStr | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title_full_unstemmed | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title_short | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets |
title_sort | endoplasmic reticulum plays a key role in α cell intracellular ca2 dynamics and glucose regulated glucagon secretion in mouse islets |
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