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Título: | The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets | Autor: | Acreman, Samuel Ma, Jinfang Denwood, Geoffrey Gao, Rui Tarasov, Andrei Rorsman, Patrik Zhang, Quan |
Palavras-chave: | Cell biology; Cellular physiology; Physiology | Data: | 17-Mai-2024 | Editora: | Elsevier | Projeto: | This study was supported by a Diabetes UK RD Lawrence Fellowship (QZ, 14/0005128), an EFSD European Research Program on New Targets for Type 2 Diabetes supported by an educational research grant from MSD (Q.Z., 96406), a John Fell Fund project grant (Q.Z., 152/052), the RCUK Medical Research Council (PR, MR/VO11979/1), the Leona M. and Harry B. Helmsley Charitable Trust (PR, G-1912-03553& G-2305-06047), and a project grant from the National Natural Science Foundation of China (82200887) to R.G.. J.M. is supported by a visiting fellowship from Chinese Scholarship Council (CSC; 202106240129). | Título da revista, periódico, livro ou evento: | iScience | Volume: | 27 | Número: | 5 | Resumo: | 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) Ca2+ on intrinsic α-cell glucagon secretion. Blocking isradipine-sensitive L-type voltage-gated Ca2+ (Cav) channels abolished α-cell electrical activity but had little impact on its cytosolic Ca2+ oscillations or low-glucose-stimulated glucagon secretion. In contrast, depleting ER Ca2+ with cyclopiazonic acid or blocking ER Ca2+-releasing ryanodine receptors abolished α-cell glucose sensitivity and low-glucose-stimulated glucagon secretion. ER Ca2+ mobilization in α-cells is regulated by intracellular ATP and likely to be coupled to Ca2+ influx through P/Q-type Cav channels. ω-Agatoxin IVA blocked α-cell ER Ca2+ 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 Ca2+ mobilization, a mechanism that can be independent of α-cell electrical activity. | URI: | https://hdl.handle.net/10316/115075 | ISSN: | 25890042 | DOI: | 10.1016/j.isci.2024.109665 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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The endoplasmic reticulum plays a key role in α-cell intracellular Ca2+ dynamics and glucose-regulated glucagon secretion in mouse islets.pdf | 2.33 MB | Adobe PDF | Ver/Abrir |
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