Morphological localisation of sulfonylurea receptor 1 in endocrine cells of human, mouse and rat pancreas.

Details

Serval ID
serval:BIB_7EE3E012EF85
Type
Article: article from journal or magazin.
Collection
Publications
Title
Morphological localisation of sulfonylurea receptor 1 in endocrine cells of human, mouse and rat pancreas.
Journal
Diabetologia
Author(s)
Guiot Y., Stevens M., Marhfour I., Stiernet P., Mikhailov M., Ashcroft S.J., Rahier J., Henquin J.C., Sempoux C.
ISSN
0012-186X (Print)
ISSN-L
0012-186X
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
50
Number
9
Pages
1889-1899
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.
Keywords
ATP-Binding Cassette Transporters/genetics, ATP-Binding Cassette Transporters/physiology, Animals, Cadaver, Humans, Islets of Langerhans/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Multidrug Resistance-Associated Proteins/deficiency, Multidrug Resistance-Associated Proteins/genetics, Pancreas/physiology, Potassium Channels/physiology, Potassium Channels, Inwardly Rectifying/physiology, Rats, Rats, Wistar, Receptors, Drug/physiology, Sulfonylurea Receptors, Tissue Donors
Pubmed
Web of science
Open Access
Yes
Create date
20/10/2016 16:10
Last modification date
20/08/2019 14:39
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