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

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 c...

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Published in:PloS one 2012-06, Vol.7 (6), p.e39462-e39462
Main Authors: Gunton, Jenny E, Sisavanh, Mary, Stokes, Rebecca A, Satin, Jon, Satin, Leslie S, Zhang, Min, Liu, Sue M, Cai, Weikang, Cheng, Kim, Cooney, Gregory J, Laybutt, D Ross, So, Trina, Molero, Juan-Carlos, Grey, Shane T, Andres, Douglas A, Rolph, Michael S, Mackay, Charles R
Format: Article
Language:English
Subjects:
Animals
B cells
Beta cells
Biochemistry
Biocompatibility
Biology
Biomedical materials
Calcium
Calcium - metabolism
Calcium channels
Calcium Signaling - genetics
Calcium signalling
Diabetes
Exocytosis
Glucose
Glucose - metabolism
Glucose Intolerance - genetics
Glucose Intolerance - metabolism
Glucose tolerance
Guanosine triphosphatases
Guanosinetriphosphatase
Handling
Homeostasis
Immunology
In vivo methods and tests
Insulin
Insulin - metabolism
Insulin Resistance - genetics
Insulin Secretion
Insulin-Secreting Cells - metabolism
Kinases
Mathematical models
Medical research
Medicine
Metabolism
Mice
Mice, Knockout
Monomeric GTP-Binding Proteins - genetics
Monomeric GTP-Binding Proteins - metabolism
Morphology
Neuroblastoma
Oscillations
Overexpression
Pharmacology
Physiology
Proteins
Rodents
Secretion
Toxicology
Transcription factors
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creator Gunton, Jenny E
Sisavanh, Mary
Stokes, Rebecca A
Satin, Jon
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Zhang, Min
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Cai, Weikang
Cheng, Kim
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Laybutt, D Ross
So, Trina
Molero, Juan-Carlos
Grey, Shane T
Andres, Douglas A
Rolph, Michael S
Mackay, Charles R
description 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. 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. 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. These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.
doi_str_mv 10.1371/journal.pone.0039462
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identifier ISSN: 1932-6203
ispartof PloS one, 2012-06, Vol.7 (6), p.e39462-e39462
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1325028263
source Publicly Available Content (ProQuest); PubMed Central
subjects Animals
B cells
Beta cells
Biochemistry
Biocompatibility
Biology
Biomedical materials
Calcium
Calcium - metabolism
Calcium channels
Calcium Signaling - genetics
Calcium signalling
Diabetes
Exocytosis
Glucose
Glucose - metabolism
Glucose Intolerance - genetics
Glucose Intolerance - metabolism
Glucose tolerance
Guanosine triphosphatases
Guanosinetriphosphatase
Handling
Homeostasis
Immunology
In vivo methods and tests
Insulin
Insulin - metabolism
Insulin Resistance - genetics
Insulin Secretion
Insulin-Secreting Cells - metabolism
Kinases
Mathematical models
Medical research
Medicine
Metabolism
Mice
Mice, Knockout
Monomeric GTP-Binding Proteins - genetics
Monomeric GTP-Binding Proteins - metabolism
Morphology
Neuroblastoma
Oscillations
Overexpression
Pharmacology
Physiology
Proteins
Rodents
Secretion
Toxicology
Transcription factors
title Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling
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