Entry
Name
Type I diabetes mellitus - Phascolarctos cinereus (koala)
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
Phascolarctos cinereus (koala) [GN:
pcw ]
Gene
110203296 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
110201282 H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752 ]
110204537 DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752 ]
110199338 rano class II histocompatibility antigen, A beta chain-like isoform X1 [KO:K06752 ]
110199339 HLA class II histocompatibility antigen, DQ beta 2 chain-like [KO:K06752 ]
110199388 H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752 ]
110199389 mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752 ]
110199403 rano class II histocompatibility antigen, A beta chain-like [KO:K06752 ]
110199459 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
110199460 HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752 ]
110208066 CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412 ]
110203128 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751 ]
110199325 BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751 ]
110199390 DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751 ]
110203695 HLA class I histocompatibility antigen, B-8 alpha chain-like [KO:K06751 ]
110223003 HLA class I histocompatibility antigen, B-40 alpha chain-like [KO:K06751 ]
110223021 HLA class I histocompatibility antigen, B-35 alpha chain-like isoform X1 [KO:K06751 ]
110223022 class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751 ]
110202415 HLA class I histocompatibility antigen, A-69 alpha chain-like isoform X1 [KO:K06751 ]
110202416 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751 ]
110218421 class I histocompatibility antigen, F10 alpha chain-like [KO:K06751 ]
110218438 major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751 ]
110218444 class I histocompatibility antigen, F10 alpha chain-like [KO:K06751 ]
110199312 H-2 class I histocompatibility antigen, D-D alpha chain-like isoform X1 [KO:K06751 ]
110218465 major histocompatibility complex class I-related gene protein-like isoform X1 [KO:K06751 ]
110199902 HLA class I histocompatibility antigen, A-11 alpha chain-like [KO:K06751 ]
110197002 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
110198951 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
pcw04660 T cell receptor signaling pathway
KO pathway
LinkDB
All DBs