Entry
Name
Type I diabetes mellitus - Leptonychotes weddellii (Weddell seal)
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
Leptonychotes weddellii (Weddell seal) [GN:
lww ]
Gene
102733188 HLA class II histocompatibility antigen, DP alpha 1 chain-like isoform X1 [KO:K06752 ]
102748173 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
102747192 HLA class II histocompatibility antigen, DQ alpha 1 chain-like [KO:K06752 ]
102734456 HLA class II histocompatibility antigen, DO alpha chain [KO:K06752 ]
102740784 HLA class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
102741082 DLA class II histocompatibility antigen, DR-1 beta chain isoform X1 [KO:K06752 ]
102747485 HLA class II histocompatibility antigen, DQ beta 2 chain isoform X1 [KO:K06752 ]
102748462 HLA class II histocompatibility antigen, DO beta chain isoform X2 [KO:K06752 ]
102750166 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
102750454 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
102742353 CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412 ]
102749162 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751 ]
102735909 H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751 ]
102746195 DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751 ]
102730025 HLA class I histocompatibility antigen, A-24 alpha chain-like [KO:K06751 ]
102736667 patr class I histocompatibility antigen, A-2 alpha chain [KO:K06751 ]
102745146 tumor necrosis factor ligand superfamily member 6-like [KO:K04389 ]
102738718 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
lww04660 T cell receptor signaling pathway
KO pathway
LinkDB
All DBs