gamma-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes
2012 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 7, 1985-1994 p.Article in journal (Refereed) Published
gamma-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. 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. The GABA signalling system was compromised in islets from type 2 diabetic individuals, where the expression of the genes encoding the alpha 1, alpha 2, beta 2 and beta 3 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. Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.
Place, publisher, year, edition, pages
2012. Vol. 55, no 7, 1985-1994 p.
gamma-Aminobutyric acid, Gene expression, Human islets, Type 2 diabetes
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-178541DOI: 10.1007/s00125-012-2548-7ISI: 000305215200017OAI: oai:DiVA.org:uu-178541DiVA: diva2:542429
De tre första författarna delar förstaförfattarskapet.2012-08-012012-07-312013-11-22Bibliographically approved