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 |
| Published: |
Cell Press
2024
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| Summary: | <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> |
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