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Enming Zhang

Research team manager

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

Author

  • Jalal Taneera
  • Z Jin
  • Yuesheng Jin
  • Sarheed Jabar Muhammed
  • Enming Zhang
  • Stefan Lang
  • S Albert Salehi
  • O Korsgren
  • Erik Renström
  • Leif Groop
  • B Birnir

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Division of Clinical Genetics
  • Islet cell physiology
  • Diabetes - Islet Patophysiology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2012

Language

English

Pages

1985-1994

Publication/Series

Diabetologia

Volume

55

Issue

7

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Gene expression
  • gamma-Aminobutyric acid
  • Human islets
  • Type 2 diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Islet cell physiology
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 1432-0428