| First Author | Le Marchand SJ | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e47084 |
| PubMed ID | 23077547 | Mgi Jnum | J:192214 |
| Mgi Id | MGI:5464178 | Doi | 10.1371/journal.pone.0047084 |
| Citation | Le Marchand SJ, et al. (2012) Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells. PLoS One 7(10):e47084 |
| abstractText | 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 alpha-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 alpha-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 alpha-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 alpha-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. |
