Entry Name Type I diabetes mellitus - Zalophus californianus (California sea lion)
Description Type I diabetes mellitus is a disease that results from autoimmune destruction of the insulin-producing beta-cells. Certain beta-cell proteins act as autoantigens after being processed by antigen-presenting cell (APC), such as macrophages and dendritic cells, and presented in a complex with MHC-II molecules on the surface of the APC. Then immunogenic signals from APC activate CD4+ T cells, predominantly of the Th1 subset. Antigen-activated Th1 cells produce IL-2 and IFNgamma. They activate macrophages and cytotoxic CD8+ T cells, and these effector cells may kill islet beta-cells by one or both of two types of mechanisms: (1) direct interactions of antigen-specific cytotoxic T cells with a beta-cell autoantigen-MHC-I complex on the beta-cell, and (2) non-specific inflammatory mediators, such as free radicals/oxidants and cytokines (IL-1, TNFalpha, TNFbeta, IFNgamma).
Class Human Diseases; Endocrine and metabolic diseaseBRITE hierarchy
Pathway map Ortholog table Organism Zalophus californianus (California sea lion) [GN:
zca ]
Gene 113926580 HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752 ]
113926581 HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752 ]
113926803 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
113927163 HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752 ]
113927388 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
113926241 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
113927833 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
113927977 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
113927976 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752 ]
113927972 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
113928077 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
113928060 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
113918869 CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413 ]
113920789 CD28; LOW QUALITY PROTEIN: T-cell-specific surface glycoprotein CD28 [KO:K06470 ]
113926316 HLA class I histocompatibility antigen, A alpha chain [KO:K06751 ]
113927768 HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751 ]
113926585 HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751 ]
113915714 patr class I histocompatibility antigen, B-2 alpha chain-like [KO:K06751 ]
113915700 DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751 ]
113915741 patr class I histocompatibility antigen, A-126 alpha chain-like [KO:K06751 ]
118357226 DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751 ]
113931754 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
113921804 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
Compound Reference Authors Rabinovitch A, Suarez-Pinzon WL.
Title Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus.
Journal Reference Authors Cox NJ, Wapelhorst B, Morrison VA, Johnson L, Pinchuk L, Spielman RS, Todd JA, Concannon P
Title Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families.
Journal Reference Authors Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, Reed PW, Gough SC, Jenkins SC, Palmer SM, et al.
Title A genome-wide search for human type 1 diabetes susceptibility genes.
Journal Reference Authors Fujisawa T, Ikegami H, Kawaguchi Y, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Ueda H, Shima K, Ogihara T.
Title Class I HLA is associated with age-at-onset of IDDM, while class II HLA confers susceptibility to IDDM.
Journal Reference Authors Jaeckel E, Klein L, Martin-Orozco N, von Boehmer H.
Title Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase.
Journal Reference Authors Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS.
Title Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice.
Journal Reference Authors Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA.
Title Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope.
Journal Reference Authors Lieberman SM, DiLorenzo TP.
Title A comprehensive guide to antibody and T-cell responses in type 1 diabetes.
Journal Reference Authors Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
Title Granzyme B: a natural born killer.
Journal Related zca04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
