Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5−/− mice
Abstract
Glucose homeostasis is critically dependent on insulin release from pancreatic β-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (Vm) and the cytosolic calcium level ([Ca2+]cyt). We propose that TRPM5, a Ca2+-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca2+-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5-/- cells. Ca2+-imaging and electrophysiological analysis show that glucose-induced oscillations of Vm and [Ca2+]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.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2010
- DOI:
- 10.1073/pnas.0913107107
- Bibcode:
- 2010PNAS..107.5208C