title: γ-Aminobutyric acid (GABA) signalling in human pancreatic islets is altered in type 2 diabetes.
abstract: OBJECTIVE
  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
  Interstitial GABA activates GABA(A) channels and GABA(B) receptors and effectively modulates hormone release in islets from type 2 diabetic and normoglycaemic individuals.
authors.affiliation: Department of Clinical Sciences, Lund University Diabetes Center, University Hospital Malmö, Lund University, Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Taneera
authors.forename: Z
authors.initials: Z
authors.lastname: Jin
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: S J
authors.initials: SJ
authors.lastname: Muhammed
authors.forename: E
authors.initials: E
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Salehi
authors.forename: O
authors.initials: O
authors.lastname: Korsgren
authors.forename: E
authors.initials: E
authors.lastname: Renström
authors.forename: L
authors.initials: L
authors.lastname: Groop
authors.forename: B
authors.initials: B
authors.lastname: Birnir
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology*; D006706:Homeostasis; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011724:Pyridazines / Q000494:pharmacology*; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: D018756:GABA Antagonists; D011724:Pyridazines; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; C049853:gabazine