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

Taneera, Jalal LU ; Jin, Z; Jin, Yuesheng LU ; Jabar Muhammed, Sarheed LU ; Zhang, Enming LU ; Lang, Stefan LU ; Salehi, S Albert LU ; Korsgren, O; Renström, Erik LU and Groop, Leif LU , et al. (2012) In Diabetologia 55(7). p.1985-1994
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 GABA(A) channel subunits... (More)
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 GABA(A) 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 GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) 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 GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gene expression, gamma-Aminobutyric acid, Human islets, Type 2 diabetes
in
Diabetologia
volume
55
issue
7
pages
1985 - 1994
publisher
Springer Verlag
external identifiers
  • wos:000305215200017
  • pmid:22538358
  • scopus:84866402723
ISSN
1432-0428
DOI
10.1007/s00125-012-2548-7
language
English
LU publication?
yes
id
1e84761d-dfd9-4896-8bf6-c85987feac45 (old id 2518935)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22538358?dopt=Abstract
date added to LUP
2012-05-07 13:53:13
date last changed
2017-11-19 03:07:54
@article{1e84761d-dfd9-4896-8bf6-c85987feac45,
  abstract     = {AIMS/HYPOTHESIS: <br/><br>
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. <br/><br>
<br/><br>
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. <br/><br>
<br/><br>
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 GABA(A) 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 GABA(A) receptor antagonist, SR95531. The effects of SR95531 on hormone release revealed that activation of GABA(A) channels (GABA(A) receptors) decreased both insulin and glucagon secretion. The GABA(B) receptor antagonist, CPG55845, increased insulin release in islets (16.7 mmol/l glucose) from normoglycaemic and type 2 diabetic individuals. <br/><br>
<br/><br>
CONCLUSIONS/INTERPRETATION: Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.},
  author       = {Taneera, Jalal and Jin, Z and Jin, Yuesheng and Jabar Muhammed, Sarheed and Zhang, Enming and Lang, Stefan and Salehi, S Albert and Korsgren, O and Renström, Erik and Groop, Leif and Birnir, B},
  issn         = {1432-0428},
  keyword      = {Gene expression,gamma-Aminobutyric acid,Human islets,Type 2 diabetes},
  language     = {eng},
  number       = {7},
  pages        = {1985--1994},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes.},
  url          = {http://dx.doi.org/10.1007/s00125-012-2548-7},
  volume       = {55},
  year         = {2012},
}