title: Mouse vanin-1 is cytoprotective for islet beta cells and regulates the development of type 1 diabetes.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Aix Marseille Université, Faculté des Sciences de Luminy, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Roisin-Bouffay
authors.forename: R
authors.initials: R
authors.lastname: Castellano
authors.forename: R
authors.initials: R
authors.lastname: Valéro
authors.forename: L
authors.initials: L
authors.lastname: Chasson
authors.forename: F
authors.initials: F
authors.lastname: Galland
authors.forename: P
authors.initials: P
authors.lastname: Naquet
mesh_terms: D000581:Amidohydrolases; D000818:Animals; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D003538:Cystamine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D058851:GPI-Linked Proteins; D006706:Homeostasis / Q000502:physiology; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D018417:Th1 Cells / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D007328:Insulin; D000581:Amidohydrolases; C022314:pantetheinase; D003538:Cystamine