TY - JOUR
T1 - Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice
AU - Colsoul, Barbara
AU - Schraenen, Anica
AU - Lemaire, Katleen
AU - Quintens, Roel
AU - Van Lommel, Leentje
AU - Segal, Andrei
AU - Owsianik, Grzegorz
AU - Talavera, Karel
AU - Voets, Thomas
AU - Margolskee, Robert F.
AU - Kokrashvili, Zaza
AU - Gilon, Patrick
AU - Nilius, Bernd
AU - Schuit, Frans C.
AU - Vennekens, Rudi
A2 - Baatout, Sarah
N1 - Score=10
PY - 2010/3
Y1 - 2010/3
N2 - Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V(m)) and the cytosolic calcium level ([Ca(2+)](cyt)). We propose that TRPM5, a Ca(2+)-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca(2+)-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5(-/-) cells. Ca(2+)-imaging and electrophysiological analysis show that glucose-induced oscillations of V(m) and [Ca(2+)](cyt) have on average a reduced frequency in Trpm5(-/-) islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.
AB - Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V(m)) and the cytosolic calcium level ([Ca(2+)](cyt)). We propose that TRPM5, a Ca(2+)-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca(2+)-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5(-/-) cells. Ca(2+)-imaging and electrophysiological analysis show that glucose-induced oscillations of V(m) and [Ca(2+)](cyt) have on average a reduced frequency in Trpm5(-/-) islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.
KW - Ca2+ signaling
KW - insulin release
KW - pancreatic beta cells
KW - transient receptor potential ion channels
KW - glucose sensing
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/ezp_109384
UR - http://knowledgecentre.sckcen.be/so2/bibref/7383
U2 - 10.1073/pnas.0913107107
DO - 10.1073/pnas.0913107107
M3 - Article
SN - 0027-8424
VL - 107
SP - 5208
EP - 5213
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 11
ER -