PATHWAY: efus04940 Help
Entry
Name
Type I diabetes mellitus - Eptesicus fuscus (big brown bat)
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
Eptesicus fuscus (big brown bat) [GN:
efus ]
Gene
103303049 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
103303050 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
103304353 HLA class II histocompatibility antigen, DQ alpha 2 chain-like isoform X2 [KO:K06752 ]
103304486 HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752 ]
103304511 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752 ]
103300442 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
103295592 DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752 ]
103303036 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
103304919 DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752 ]
103303047 HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
103304352 SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752 ]
129150533 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
103303048 RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752 ]
103303037 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
103304354 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
103304514 SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752 ]
103290800 CD86; T-lymphocyte activation antigen CD86 isoform X8 [KO:K05413 ]
103301649 class I histocompatibility antigen, Gogo-C*0203 alpha chain-like [KO:K06751 ]
103300539 patr class I histocompatibility antigen, B-1 alpha chain-like isoform X1 [KO:K06751 ]
103283920 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751 ]
129147051 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751 ]
129147596 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751 ]
129147597 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751 ]
103304883 saoe class I histocompatibility antigen, A alpha chain-like isoform X1 [KO:K06751 ]
103304180 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751 ]
114229892 class I histocompatibility antigen, Gogo-B*0102 alpha chain-like [KO:K06751 ]
129147115 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751 ]
129147758 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751 ]
103304812 patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751 ]
103304966 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751 ]
103304787 saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751 ]
114229502 saoe class I histocompatibility antigen, A alpha chain-like isoform X1 [KO:K06751 ]
114229990 patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751 ]
103304222 BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751 ]
103289966 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
103296397 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 pathway
KO pathway
LinkDB
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