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PLoS One. 2012;7(10):e47084. doi: 10.1371/journal.pone.0047084. Epub 2012 Oct 15.

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

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, USA.

Abstract

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.

PMID:
23077547
PMCID:
PMC3471958
DOI:
10.1371/journal.pone.0047084
[Indexed for MEDLINE]
Free PMC Article

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