Entry
Name
Type I diabetes mellitus - Gracilinanus agilis (agile gracile opossum)
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
Gracilinanus agilis (agile gracile opossum) [GN:
gas ]
Gene
123256290 LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR beta 4 chain-like [KO:K06752 ]
123245189 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
123245190 mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
123245191 H-2 class II histocompatibility antigen, A-U alpha chain-like [KO:K06752 ]
123245192 RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752 ]
123245340 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
123245626 H-2 class II histocompatibility antigen, E-S beta chain-like isoform X1 [KO:K06752 ]
123245629 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
123246365 H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752 ]
123246408 LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
123246413 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
123246951 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
123255734 LOW QUALITY PROTEIN: major histocompatibility complex class I-related gene protein-like [KO:K06751 ]
123243714 HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751 ]
123245212 class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751 ]
123245214 class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751 ]
123245219 patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751 ]
123234496 class I histocompatibility antigen, F10 alpha chain-like [KO:K06751 ]
123246364 class I histocompatibility antigen, Gogo-B*0201 alpha chain-like [KO:K06751 ]
123245896 FASLG; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
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
gas04660 T cell receptor signaling pathway
KO pathway
LinkDB
All DBs