title: Islet glia, neurons, and beta cells.
abstract: Type 1 diabetes (T1D) is caused by autoimmune beta cell destruction. The early events triggering T1D and the forces that keep diabetic autoimmunity pancreas specific have been unclear. Our discovery that autoimmune islet destruction is not beta-cell-exclusive but includes cytotoxic T cell targeting of peri-islet glia, evoked the possibility that T1D pathogenesis may involve neuronal elements beyond beta cell/immune interactions. Recently, we have found that sensory afferent neurons are a critical component in prediabetes initiation, promoting islet inflammation through altered glucose homeostasis and progressive beta cell stress. These factors orchestrate a catastrophic cascade culminating in insulin insufficiency mediated by an autoimmune-prone host. This neuro-immuno-endocrinological triad explains diabetic inflammation as a consequence of local neuropeptide deficiency, leading to an innovative concept of disease pathogenesis with novel therapeutic implications.
authors.affiliation: Departments of Pediatrics and Immunology, The Hospital for Sick Children, Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hubert
authors.initials: H
authors.lastname: Tsui
authors.forename: Shawn
authors.initials: S
authors.lastname: Winer
authors.forename: Yin
authors.initials: Y
authors.lastname: Chan
authors.forename: Dorothy
authors.initials: D
authors.lastname: Truong
authors.forename: Lan
authors.initials: L
authors.lastname: Tang
authors.forename: Jason
authors.initials: J
authors.lastname: Yantha
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Paltser
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Dosch
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000294:innervation*; D051379:Mice; D016688:Mice, Inbred NOD; D008954:Models, Biological; D009457:Neuroglia / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010179:Pancreas / Q000294:innervation / Q000473:pathology