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Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling

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.

Type Journal
Authors 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.:
Garvan Authors Prof Gregory Cooney , Prof Jenny Gunton , A/Prof Ross Laybutt , A/Prof Shane Grey
Publisher Name PLoS ONE
Published Date 2012-06-28 00:00:00
Published Volume 7
Published Issue 6
Published Pages e39462
URL http://www.ncbi.nlm.nih.gov/pubmed/22761801
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11432_12014/12 Gunton PlosOne_.pdf