u03b3-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes
| Autor: | Stefan Lang, Leif Groop, Enming Zhang, Yuesheng Jin, Erik Renström, Bryndis Birnir, Jalal Taneera, S Albert Salehi, Zhe Jin, Olle Korsgren, Sarheed Jabar Muhammed |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Endocrinology Diabetes and Metabolism Down-Regulation Biology Aminobutyric acid gamma-Aminobutyric acid Article GABA Antagonists 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Internal medicine Insulin-Secreting Cells Internal Medicine medicine Homeostasis Humans γ-Aminobutyric acid Receptor gamma-Aminobutyric Acid 030304 developmental biology Human islets 0303 health sciences Dose-Response Relationship Drug Pancreatic islets Type 2 diabetes GABA receptor antagonist Middle Aged Immunohistochemistry 3. Good health Pyridazines Endocrinology medicine.anatomical_structure nervous system Diabetes Mellitus Type 2 Receptors GABA-B Disease Progression Female Gene expression Signal transduction 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Diabetologia |
| Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2548-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users. |
| Databáze: | OpenAIRE |
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