Entry Name Type I diabetes mellitus - Ovis aries (sheep)
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 Ovis aries (sheep) [GN:
oas ]
Gene 101108696 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
101108962 DQA; HLA class II histocompatibility antigen, DQ alpha 2 chain precursor [KO:K06752 ]
101119342 OVAR-DRB1; DLA class II histocompatibility antigen, DR-1 beta chain-like precursor [KO:K06752 ]
101109747 mamu class II histocompatibility antigen, DR alpha chain-like precursor [KO:K06752 ]
101108961 DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X2 [KO:K06752 ]
101109219 HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752 ]
101109746 HLA class II histocompatibility antigen, DM beta chain isoform X2 [KO:K06752 ]
101110545 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
101116099 HLA class II histocompatibility antigen, DM alpha chain isoform X2 [KO:K06752 ]
101114758 LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
101118514 boLa class II histocompatibility antigen, DQB*0101 beta chain isoform X2 [KO:K06752 ]
101120392 boLa class II histocompatibility antigen, DQB*0101 beta chain isoform X2 [KO:K06752 ]
101115073 rano class II histocompatibility antigen, A beta chain isoform X1 [KO:K06752 ]
554317 CD80; T-lymphocyte activation antigen CD80 precursor [KO:K05412 ]
554318 CD86; T-lymphocyte activation antigen CD86 precursor [KO:K05413 ]
443480 CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470 ]
443064 IL12A; interleukin-12 subunit alpha precursor [KO:K05406 ]
443472 IL12B; interleukin-12 subunit beta precursor [KO:K05425 ]
101107908 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X4 [KO:K06751 ]
106990117 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X4 [KO:K06751 ]
101107641 BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X1 [KO:K06751 ]
101119545 BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751 ]
101104866 LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-6 [KO:K06751 ]
101111694 LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751 ]
101112480 H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X2 [KO:K06751 ]
114109630 BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X6 [KO:K06751 ]
101105609 LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7 [KO:K06751 ]
132658253 BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
100135696 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
100144426 FAS; tumor necrosis factor receptor superfamily member 6 precursor [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 oas04660 T cell receptor signaling pathway
KO pathway LinkDB All DBs
