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Diabetologia
Published in: Diabetologia 7/2012

Open Access 01-07-2012 | Article

γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes

Authors: J. Taneera, Z. Jin, Y. Jin, S. J. Muhammed, E. Zhang, S. Lang, A. Salehi, O. Korsgren, E. Renström, L. Groop, B. Birnir

Published in: Diabetologia | Issue 7/2012

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Abstract

Aims/hypothesis

γ-Aminobutyric acid (GABA) is a signalling molecule in the interstitial space in pancreatic islets. We examined the expression and function of the GABA signalling system components in human pancreatic islets from normoglycaemic and type 2 diabetic individuals.

Methods

Expression of GABA signalling system components was studied by microarray, quantitative PCR analysis, immunohistochemistry and patch-clamp experiments on cells in intact islets. Hormone release was measured from intact islets.

Results

The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the α1, α2, β2 and β3 GABAA channel subunits was downregulated. GABA originating within the islets evoked tonic currents in the cells. The currents were enhanced by pentobarbital and inhibited by the GABAA receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABAA channels (GABAA receptors) decreased both insulin and glucagon secretion. The GABAB receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals.

Conclusions/interpretation

Interstitial GABA activates GABAA channels and GABAB receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.
Appendix
Available only for authorised users
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Metadata
Title
γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes
Authors
J. Taneera
Z. Jin
Y. Jin
S. J. Muhammed
E. Zhang
S. Lang
A. Salehi
O. Korsgren
E. Renström
L. Groop
B. Birnir
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2548-7

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