Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

Le Marchand SJ, Piston DW
PLoS One. 2012 7 (10): e47084

PMID: 23077547 · PMCID: PMC3471958 · DOI:10.1371/journal.pone.0047084

The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+)](i)) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+)](i) and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP) channel activity but not on tetrodotoxin-sensitive Na(+) channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+)](i) and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP) channel activity or reduction in α-cell [Ca(2+)](i). Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+)](i) and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

MeSH Terms (14)

Animals Arginine Calcium Calcium Signaling Glucagon Glucagon-Secreting Cells Glucose Mice Mice, Inbred C57BL Mice, Transgenic Potassium Channels Sodium Channel Blockers Sodium Channels Tetrodotoxin

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