title: Morphological localisation of sulfonylurea receptor 1 in endocrine cells of human, mouse and rat pancreas.
abstract: OBJECTIVE
  Sulfonylurea receptor 1 (SUR1) is the regulatory subunit of ATP-sensitive K channels in beta cells. Morphological methods (immunohistochemistry and sulfonylurea binding) were used to establish the cellular and subcellular location of SUR1 in human and rodent islets.
  
  
  RESULTS
  In the human, mouse and rat pancreas, all endocrine cells of the islets were immunolabelled with an anti-SUR1 antibody, whereas tissues containing SUR2 were consistently negative, as were those from Sur1 (also known as Abcc8)(-/-) mice. In beta cells of the three species, the plasma membrane was distinctly stained, but SUR1 was mainly present over the cytoplasm, with an intensity that varied between cells. Electron microscopy showed that SUR1 was immunolocalised in insulin, glucagon and somatostatin granules. In rat beta cells degranulated by in vivo treatment with glibenclamide (known as glyburide in the USA and Canada), the insulin and SUR1 staining intensity was similarly decreased by approximately 45%, whereas SUR1 staining was not changed in non-beta cells. In all islet cells, binding of glibenclamide labelled with fluorescent dipyrromethane boron difluoride (BODIPY-FL) was punctate over the cytoplasm, compatible with the labelling of endocrine granules. A faint labelling persisted in Sur1 (-/-) mice, but it was not different from that obtained with BODIPY-FL alone used as negative control.
  
  
  CONCLUSIONS
  Our study immunolocalised SUR1 in alpha, beta and delta cells of human, mouse and rat islets, and for the first time visualised it in the plasma membrane. We also show that SUR1 is abundant in endocrine granules, where its function remains to be established. No specific sulfonylurea-binding sites other than SUR1 are identified in islet cells by the glibenclamide-BODIPY-FL technique.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Louvain, B-1200, Brussels, Belgium. guiot@anps.ucl.ac.be.
authors.forename: Y
authors.initials: Y
authors.lastname: Guiot
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Louvain, B-1200, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Stevens
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Louvain, B-1200, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Marhfour
authors.affiliation: Endocrinology Unit and Metabolism, Faculty of Medicine, University of Louvain, UCL5530, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Stiernet
authors.affiliation: Physiology Laboratory, University of Oxford, Oxford, UK.
authors.forename: M
authors.initials: M
authors.lastname: Mikhailov
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
authors.forename: S J H
authors.initials: SJH
authors.lastname: Ashcroft
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Louvain, B-1200, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Rahier
authors.affiliation: Endocrinology Unit and Metabolism, Faculty of Medicine, University of Louvain, UCL5530, Brussels, Belgium.
authors.forename: J-C
authors.initials: JC
authors.lastname: Henquin
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Louvain, B-1200, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Sempoux
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002102:Cadaver; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010179:Pancreas / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000502:physiology*; D064233:Sulfonylurea Receptors; D014019:Tissue Donors
chemical_list: D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; C577507:ABCC8 protein, human; C577510:ABCC9 protein, human; C577508:Abcc8 protein, mouse; C577509:Abcc8 protein, rat; C577512:Abcc9 protein, rat