Entry Name Type I diabetes mellitus - Ursus americanus (American black bear)
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 Ursus americanus (American black bear) [GN:
uar ]
Gene 123794091 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
123794092 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
123790938 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
123790941 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
123790942 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
123790948 HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752 ]
123790949 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
123790950 boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752 ]
123790951 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
123790953 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
123790954 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
123791051 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752 ]
123802090 CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413 ]
123785045 class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751 ]
123793445 HLA class I histocompatibility antigen, B alpha chain-like [KO:K06751 ]
123780238 H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751 ]
123791023 patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751 ]
123791025 LOW QUALITY PROTEIN: class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751 ]
123791026 DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751 ]
123791029 DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751 ]
123803052 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
123795545 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 uar04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
