title: Insulinoma-associated protein 2-deficient mice develop severe forms of diabetes induced by multiple low doses of streptozotocin.
abstract: Insulinoma-associated protein 2 (IA-2) is the major autoantigen that contributes to the pathogenesis of type 1 diabetes (T1D). IA-2-deficient (IA-2-/-) mice showed impaired insulin secretion after intraperitoneal injection of glucose as well as elevated glucose level in a glucose tolerance test. Despite the fact that 70% of newly diagnosed T1D patients have an antibody against IA-2, the role of IA-2 in the pathogenesis of T1D is largely unknown. In this study, the sensitivity to diabetes induced by streptozotocin (STZ) of IA-2-/- mice was compared with that of wild-type (WT) mice. STZ injection to IA-2-/- mice caused significant elevation of blood glucose and depressed insulin concentration in the pancreas. Furthermore, abnormal ultrastructure in the beta cells of the IA-2-/- mice was revealed by electron microscopy, showing a decreased number of insulin containing vesicles and dilation of the ER-Golgi complex. These results demonstrated that IA-2-/- mice had higher sensitivity to STZ, suggesting a role of IA-2 not only in the secretion but also in the production of insulin.
authors.affiliation: Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakajima
authors.forename: Guoying
authors.initials: G
authors.lastname: Wu
authors.forename: Natsumi
authors.initials: N
authors.lastname: Takeyama
authors.forename: Akikazu
authors.initials: A
authors.lastname: Sakudo
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sugiura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yukawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Onodera
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000235:genetics / Q000502:physiology*; D013311:Streptozocin
chemical_list: D001324:Autoantigens; D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8