title: Nonobese diabetic (NOD) mouse dendritic cells stimulate insulin secretion by prediabetic islets.
abstract: In the Nonobese diabetic (NOD) mouse, a spontaneous model of type 1 diabetes, the pathogenic process is classically thought to start at 3-4 weeks of age with an accumulation of antigen-presentingcells (APC), especially CD11c+ dendritic cells (DC), around the pancreatic islets of Langerhans. Concomitantly, hyperinsulinemia and slight hyperglucagonemia are observed, which may be either the cause or consequence of the initial APC infiltration. To determine whether infiltrating DC can affect islet activity in control (C57BL/6) and NOD mice, we performed experiments in which islets and DC were isolated and co-cultured. We first showed that, immediately after isolation, islets from 8-week-old prediabetic NOD mice had significantly higher insulin and glucagon contents than those from C57BL/6 controls. Moreover, as is the case in vivo, prediabetic NOD mouse islets secrete more insulin in vitro at 11.1 mM glucose than C57BL/6 ones. In DC-islet co-cultures, insulin secretion was significantly increased for NOD mice only, while that of glucagon was not significantly affected. These findings indicate that NOD DC are good candidates for stimulating the NOD mouse beta-cell hyperactivity that is observed both in vivo and in vitro, and might, consequently, sensitize NOD islets to an autoimmune attack.
authors.affiliation: CNRS UMR 8603, University Paris V, Necker Hospital, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Durant
authors.forename: Véronique
authors.initials: V
authors.lastname: Alves
authors.forename: Josiane
authors.initials: J
authors.lastname: Coulaud
authors.forename: Françoise
authors.initials: F
authors.lastname: Homo-Delarche
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000378:metabolism*; D011863:Radioimmunoassay
chemical_list: D007328:Insulin; D005934:Glucagon