Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells

Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo mode...

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Autores: Torrejón-Escribano, Benjamín, Escoriza, Jessica, Montanya Mias, Eduard, Blasi Cabús, Joan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/134283
Acceso en línea:https://hdl.handle.net/2445/134283
Access Level:acceso abierto
Palabra clave:Glucosa
Farmacologia
Insulina
Farmacocinètica
Metabolisme
Proteïnes SNARE
Cèl·lules B
Glucose
Pharmacology
Insulin
Pharmacokinetics
Metabolism
SNARE Proteins
B cells
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spelling Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cellsTorrejón-Escribano, BenjamínEscoriza, JessicaMontanya Mias, EduardBlasi Cabús, JoanGlucosaFarmacologiaInsulinaFarmacocinèticaMetabolismeProteïnes SNARECèl·lules BGlucosePharmacologyInsulinPharmacokineticsMetabolismSNARE ProteinsB cellsProlonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/ vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucoseinduced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.Association for the Study of Internal Secretions2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/134283Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1210/en.2010-0898Endocrinology, 2011, vol. 152, num. 4, p. 1290-1299https://doi.org/10.1210/en.2010-0898(c) Association for the Study of Internal Secretions, 2011info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1342832026-05-27T06:46:51Z
dc.title.none.fl_str_mv Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
title Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
spellingShingle Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
Torrejón-Escribano, Benjamín
Glucosa
Farmacologia
Insulina
Farmacocinètica
Metabolisme
Proteïnes SNARE
Cèl·lules B
Glucose
Pharmacology
Insulin
Pharmacokinetics
Metabolism
SNARE Proteins
B cells
title_short Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
title_full Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
title_fullStr Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
title_full_unstemmed Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
title_sort Glucose-dependent changes in SNARE proyein levels in pancreatic beta-cells
dc.creator.none.fl_str_mv Torrejón-Escribano, Benjamín
Escoriza, Jessica
Montanya Mias, Eduard
Blasi Cabús, Joan
author Torrejón-Escribano, Benjamín
author_facet Torrejón-Escribano, Benjamín
Escoriza, Jessica
Montanya Mias, Eduard
Blasi Cabús, Joan
author_role author
author2 Escoriza, Jessica
Montanya Mias, Eduard
Blasi Cabús, Joan
author2_role author
author
author
dc.subject.none.fl_str_mv Glucosa
Farmacologia
Insulina
Farmacocinètica
Metabolisme
Proteïnes SNARE
Cèl·lules B
Glucose
Pharmacology
Insulin
Pharmacokinetics
Metabolism
SNARE Proteins
B cells
topic Glucosa
Farmacologia
Insulina
Farmacocinètica
Metabolisme
Proteïnes SNARE
Cèl·lules B
Glucose
Pharmacology
Insulin
Pharmacokinetics
Metabolism
SNARE Proteins
B cells
description Prolonged exposure to high glucose concentration alters the expression of a set of proteins in pancreatic-cells and impairs their capacity to secrete insulin. The cellular and molecular mechanisms that lie behind this effect are poorly understood. In this study, three either in vitro or in vivo models (cultured rat pancreatic islets incubated in high glucose media, partially pancreatectomized rats, and islets transplanted to streptozotozin-induced diabetic mice) were used to evaluate the dependence of the biological model and the treatment, together with the cell location (insulin granule or plasma membrane) of the affected proteins and the possible effect of sustained insulin secretion, on the glucose-induced changes in protein expression. In all three models, islets exposed to high glucose concentrations showed a reduced expression of secretory granule associated vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin/ vesicle-associated membrane protein 2 and cellubrevin but minor or no significant changes in the expression of the membrane-associated target-SNARE proteins syntaxin1 and synaptosomal associated protein-25 and a marked increase in the expression of synaptosomal-associated protein-23 protein. The inhibition of insulin secretion by the L-type voltage-dependent calcium channel nifedipine or the potassium channel activator diazoxide prevented the glucoseinduced reduction in islet insulin content but not in vesicle-SNARE proteins, indicating that the granule depletion due to sustained exocytosis was not involved in the changes of protein expression induced by high glucose concentration. Altogether, the results suggest that high glucose has a direct toxic effect on the secretory pathway by decreasing the expression of insulin granule SNARE-associated proteins.
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/134283
url https://hdl.handle.net/2445/134283
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1210/en.2010-0898
Endocrinology, 2011, vol. 152, num. 4, p. 1290-1299
https://doi.org/10.1210/en.2010-0898
dc.rights.none.fl_str_mv (c) Association for the Study of Internal Secretions, 2011
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Association for the Study of Internal Secretions, 2011
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Association for the Study of Internal Secretions
publisher.none.fl_str_mv Association for the Study of Internal Secretions
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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