The direct effects of tacrolimus and cyclosporin A on isolated human islets: A functional, survival and gene expression study.

Détails

ID Serval
serval:BIB_FD998CF204E3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The direct effects of tacrolimus and cyclosporin A on isolated human islets: A functional, survival and gene expression study.
Périodique
Islets
Auteur(s)
Bugliani M., Masini M., Liechti R., Marselli L., Xenarios I., Boggi U., Filipponi F., Masiello P., Marchetti P.
ISSN
1938-2022 (Electronic)
Statut éditorial
Publié
Date de publication
2009
Volume
1
Numéro
2
Pages
106-110
Langue
anglais
Résumé
The use of immunosuppressive drugs in transplanted patients is associated with the development of diabetes, possibly due to β-cell toxicity. To better understand the mechanisms leading to post-transplant diabetes, we investigated the actions of prolonged exposure of isolated human islets to therapeutical levels of tacrolimus (Tac) or cyclosporin A (CsA). Islets were isolated from the pancreas of multiorgan donors by enzymatic digestion and density gradient centrifugation. Functional, survival and molecular studies were then performed after 4 days of incubation with therapeutical concentrations of Tac or  CsA. Glucose-induced insulin secretion was significantly decreased in Tac, but not in CsA exposed islets, which was associated with a reduction of the amount of insulin granules as shown by electron microscopy. The percentage of apoptotic β-cells was higher in Tac than CsA exposed islets. Microarray experiments followed by Gene Set Enrichment Analysis revealed that gene expression was more markedly affected upon Tac treatment. In conclusion, Tac and CsA affect features of beta-cell differently, with several changes occurring at the molecular level.
Mots-clé
Aged, Cell Separation, Cell Survival/drug effects, Cell Survival/genetics, Cells, Cultured, Cyclosporine/pharmacology, Female, Gene Expression/drug effects, Gene Expression Profiling, Humans, Immunosuppressive Agents/pharmacology, Islets of Langerhans/drug effects, Islets of Langerhans/metabolism, Male, Microarray Analysis, Middle Aged, Tacrolimus/pharmacology
Pubmed
Web of science
Création de la notice
17/10/2012 11:58
Dernière modification de la notice
20/08/2019 16:28
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