Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/120921
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Type: Journal article
Title: Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling
Author: Gunton, J.E.
Sisavanh, M.
Stokes, R.A.
Satin, J.
Satin, L.S.
Zhang, M.
Liu, S.M.
Cai, W.
Cheng, K.
Cooney, G.J.
Laybutt, D.R.
So, T.
Molero, J.C.
Grey, S.T.
Andres, D.A.
Rolph, M.S.
Mackay, C.R.
Citation: PLoS One, 2012; 7(6):e39462-1-e39462-9
Publisher: PLoS - Public Library of Science
Issue Date: 2012
ISSN: 1932-6203
1932-6203
Editor: Planas, J.V.
Statement of
Responsibility: 
Jenny E. Gunton, Mary Sisavanh, Rebecca A. Stokes, Jon Satin, Leslie S. Satin, Min Zhang, Sue M. Liu, Weikang Cai, Kim Cheng, Gregory J. Cooney, D. Ross Laybutt, Trina So, Juan- Carlos Molero, Shane T. Grey, Douglas A. Andres, Michael S. Rolph, Charles R. Mackay
Abstract: Aims and Hypopthesis: 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.
Keywords: Glucose intolerance
Rights: © 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.
DOI: 10.1371/journal.pone.0039462
Grant ID: NHMRC
Published version: http://dx.doi.org/10.1371/journal.pone.0039462
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