Entry Name Type I diabetes mellitus - Marmota marmota marmota (Alpine marmot)
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).
Class Human Diseases; Endocrine and metabolic diseaseBRITE hierarchy
Pathway map Ortholog table Organism Marmota marmota marmota (Alpine marmot) [GN:
mmma ]
Gene 107143604 HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
107143767 mamu class II histocompatibility antigen, DR alpha chain [KO:K06752 ]
107143768 HLA class II histocompatibility antigen, DRB1 beta chain-like isoform X1 [KO:K06752 ]
107143770 HLA class II histocompatibility antigen, DRB1 beta chain-like isoform X1 [KO:K06752 ]
107143774 HLA class II histocompatibility antigen, DO beta chain-like isoform X1 [KO:K06752 ]
107143780 HLA class II histocompatibility antigen, DM beta chain [KO:K06752 ]
107143781 HLA class II histocompatibility antigen, DM alpha chain [KO:K06752 ]
107143799 HLA class II histocompatibility antigen, DP alpha 1 chain isoform X1 [KO:K06752 ]
107143800 HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752 ]
107144062 HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752 ]
107143602 HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752 ]
107143249 Cd86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413 ]
107138627 Cd28; T-cell-specific surface glycoprotein CD28 isoform X2 [KO:K06470 ]
107143708 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X11 [KO:K06751 ]
107143771 patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751 ]
107134844 popy Class I histocompatibility antigen, A-1 alpha chain-like [KO:K06751 ]
107160421 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X1 [KO:K06751 ]
107160437 saoe class I histocompatibility antigen, A alpha chain-like isoform X1 [KO:K06751 ]
107160471 HLA class I histocompatibility antigen, B alpha chain-like [KO:K06751 ]
107160568 H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751 ]
107160834 patr class I histocompatibility antigen, CH28 alpha chain-like isoform X1 [KO:K06751 ]
107160869 class I histocompatibility antigen, Gogo-OKO alpha chain-like isoform X3 [KO:K06751 ]
107143586 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751 ]
125617671 H-2 class I histocompatibility antigen, alpha chain-like [KO:K06751 ]
107160418 patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751 ]
107147374 Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
107153328 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 KO pathway LinkDB All DBs
