Entry Name Type I diabetes mellitus - Physeter catodon (sperm whale)
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 Physeter catodon (sperm whale) [GN:
pcad ]
Gene 102994322 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
102973944 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
102976012 HLA class II histocompatibility antigen, DQ beta 1 chain isoform X2 [KO:K06752 ]
102973764 DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752 ]
102976287 HLA class II histocompatibility antigen, DQ alpha 2 chain isoform X2 [KO:K06752 ]
102992942 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
102974479 HLA class II histocompatibility antigen, DO beta chain [KO:K06752 ]
102994605 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
102978546 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
102975720 CD80; T-lymphocyte activation antigen CD80 isoform X2 [KO:K05412 ]
102974216 CD28; LOW QUALITY PROTEIN: T-cell-specific surface glycoprotein CD28 [KO:K06470 ]
112064291 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X2 [KO:K06751 ]
112064292 BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
112064318 BOLA class I histocompatibility antigen, alpha chain BL3-6-like [KO:K06751 ]
102996245 LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
102985933 H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751 ]
102979864 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
102985097 FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [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 KO pathway LinkDB All DBs
