TY - JOUR
T1 - Glucose Decouples Intracellular Ca2+ Activity from Glucagon Secretion in Mouse Pancreatic Islet Alpha-Cells
AU - Le Marchand, Sylvain J.
AU - Piston, David W.
N1 - Funding Information:
Equipment and technical assistance were provided by the Vanderbilt Islet Procurement and Analysis, and Hormone Assay cores (supported by the Vanderbilt Diabetes Center (DK20593), the Vanderbilt Ingram Cancer Center (CA68485), and the Vanderbilt Digestive Disease Research Center (DK58404)).
PY - 2012/10/15
Y1 - 2012/10/15
N2 - The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca2+]i) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca2+]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 KATP channel activity but not on tetrodotoxin-sensitive Na+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca2+]i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by KATP channel activity or reduction in α-cell [Ca2+]i. Our results demonstrate that glucose uncouples the positive relationship between [Ca2+]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.
AB - The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca2+]i) and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca2+]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 KATP channel activity but not on tetrodotoxin-sensitive Na+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca2+]i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by KATP channel activity or reduction in α-cell [Ca2+]i. Our results demonstrate that glucose uncouples the positive relationship between [Ca2+]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.
UR - http://www.scopus.com/inward/record.url?scp=84867513391&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0047084
DO - 10.1371/journal.pone.0047084
M3 - Article
C2 - 23077547
AN - SCOPUS:84867513391
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 10
M1 - e47084
ER -