Document Type
Article
Original Publication Date
2012
Journal/Book/Conference Title
PLOS ONE
Volume
7
DOI of Original Publication
10.1371/journal.pone.0039462
Date of Submission
November 2014
Abstract
Aims and Hypothesis
Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.
Methods
Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets.
Results
Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency.
Conclusions
These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.
Rights
Copyright: © 2012 Gunton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Is Part Of
VCU Pharmacology and Toxicology Publications
Comments
Originally Published at http://dx.doi.org/10.1371/journal.pone.0039462