PATHWAY: bta04940 Help
Entry
Name
Type I diabetes mellitus - Bos taurus (cow)
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).
Type I diabetes is a polygenic disease. One of the principle determining genetic factors in diabetes incidence is the inheritance of mutant MHC-II alleles. Another plausible candidate gene is the insulin gene.
Class
Human Diseases; Endocrine and metabolic disease
BRITE hierarchy
Pathway map
Ortholog table
Organism
Bos taurus (cow) [GN:
bta ]
Gene
282490 BOLA-DMA; HLA class II histocompatibility antigen, DM alpha chain precursor [KO:K06752 ]
282491 BOLA-DMB; major histocompatibility complex, class II, DM beta precursor [KO:K06752 ]
282493 BOLA-DOB; HLA class II histocompatibility antigen, DO beta chain precursor [KO:K06752 ]
282494 BOLA-DQA5; major histocompatibility complex, class II, DQ alpha 5 precursor [KO:K06752 ]
282495 BOLA-DQB; major histocompatibility complex, class II, DQ beta precursor [KO:K06752 ]
282498 BOLA-DYB; major histocompatibility complex, class II, DY beta precursor [KO:K06752 ]
282535 BOLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752 ]
282530 BOLA-DRB3; major histocompatibility complex, class II, DRB3 [KO:K06752 ]
525727 BOLA-DOA; HLA class II histocompatibility antigen, DO alpha chain precursor [KO:K06752 ]
506214 BOLA-DRA; major histocompatibility complex, class II, DR alpha precursor [KO:K06752 ]
539241 BLA-DQB; boLa class II histocompatibility antigen, DQB*0101 beta chain precursor [KO:K06752 ]
100848815 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like precursor [KO:K06752 ]
282497 BOLA-DYA; major histocompatibility complex, class II, DY alpha precursor [KO:K06752 ]
538700 BOLA-DRB2; HLA class II histocompatibility antigen, DR beta 5 chain isoform X3 [KO:K06752 ]
407131 CD80; T-lymphocyte activation antigen CD80 [KO:K05412 ]
414345 CD86; T-lymphocyte activation antigen CD86 [KO:K05413 ]
281050 CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470 ]
281856 IL12A; interleukin-12 subunit alpha precursor [KO:K05406 ]
281857 IL12B; interleukin-12 subunit beta precursor [KO:K05425 ]
512672 major histocompatibility complex, class I precursor [KO:K06751 ]
515712 BOLA; MHC class I heavy chain isoform 1 precursor [KO:K06751 ]
767904 MGC126945; LOW QUALITY PROTEIN: uncharacterized protein LOC767904 [KO:K06751 ]
507917 BOLA class I histocompatibility antigen, alpha chain BL3-6 isoform X1 [KO:K06751 ]
510417 BOLA-NC1; non-classical MHC class I antigen precursor [KO:K06751 ]
533050 BoLA; major histocompatibility complex, class I, A precursor [KO:K06751 ]
616942 major histocompatibility complex, class I, A-like precursor [KO:K06751 ]
407111 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
282488 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 pathway
bta04660 T cell receptor signaling pathway
KO pathway
LinkDB
All DBs