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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2518935
- author
- 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. (More)
- 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
; Groop, Leif
LU
and Birnir, B
(Less)
- organization
- publishing date
- 2012
- 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
- external identifiers
-
- wos:000305215200017
- pmid:22538358
- scopus:84866402723
- pmid:22538358
- 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
- 2016-04-01 10:14:21
- date last changed
- 2024-04-07 03:25:36
@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}},
keywords = {{Gene expression; gamma-Aminobutyric acid; Human islets; Type 2 diabetes}},
language = {{eng}},
number = {{7}},
pages = {{1985--1994}},
publisher = {{Springer}},
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}},
doi = {{10.1007/s00125-012-2548-7}},
volume = {{55}},
year = {{2012}},
}