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Diabetologia
Erschienen in: Diabetologia 7/2008

01.07.2008 | Article

Mouse vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes

verfasst von: C. Roisin-Bouffay, R. Castellano, R. Valéro, L. Chasson, F. Galland, P. Naquet

Erschienen in: Diabetologia | Ausgabe 7/2008

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Abstract

Aims/hypothesis

Islet cell death is a key initiating and perpetuating event in type 1 diabetes and involves both immune-mediated and endogenous mechanisms. The epithelial pantetheinase vanin-1 is proinflammatory and cytoprotective via cysteamine release in some tissues. We investigated the impact of a vanin-1 deficiency on islet death and type 1 diabetes incidence.

Methods

Vanin-1-deficient mice were produced and tested in drug-induced and autoimmune diabetes models. The contribution of vanin-1 to islet survival versus immune responses was evaluated using lymphocyte transfer and islet culture experiments.

Results

The vanin-1/cysteamine pathway contributes to the protection of islet beta cells from streptozotocin-induced death in vitro and in vivo. Furthermore, vanin-1-deficient NOD mice showed a significant aggravation of diabetes, which depended upon loss of vanin-1 expression by host tissues. This increased islet fragility was accompanied by greater CD4+ insulitis without impairment of regulatory cells. Addition of cystamine, the product of pantetheinase activity, protected islets in vitro and compensated for vanin-1 deficiency in vivo.

Conclusions/interpretation

This study unravels a major cytoprotective role of cysteamine for islet cells and suggests that modulation of pantetheinase activity may offer alternative strategies to maintain islet cell homeostasis.
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Metadaten
Titel
Mouse vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes
verfasst von
C. Roisin-Bouffay
R. Castellano
R. Valéro
L. Chasson
F. Galland
P. Naquet
Publikationsdatum
01.07.2008
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 7/2008
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-008-1017-9

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