PATHWAY: panu04940 Help
Entry
Name
Type I diabetes mellitus - Papio anubis (olive baboon)
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
Papio anubis (olive baboon) [GN:
panu ]
Gene
110743061 HLA class II histocompatibility antigen, DO beta chain [KO:K06752 ]
103883612 HLA class II histocompatibility antigen, DM alpha chain isoform X2 [KO:K06752 ]
101016766 HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752 ]
101017941 HLA class II histocompatibility antigen, DO alpha chain isoform X7 [KO:K06752 ]
101014430 HLA class II histocompatibility antigen, DRB1-15 beta chain isoform X1 [KO:K06752 ]
116268485 HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752 ]
101018551 HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752 ]
101000981 HLA class II histocompatibility antigen, DP beta 1 chain-like precursor [KO:K06752 ]
101018895 HLA class II histocompatibility antigen, DP alpha 1 chain precursor [KO:K06752 ]
100126740 CD28; T-cell-specific surface glycoprotein CD28 precursor [KO:K06470 ]
101021987 HLA class I histocompatibility antigen, B-27 alpha chain isoform X1 [KO:K06751 ]
101019755 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, B-38 alpha chain [KO:K06751 ]
101025045 patr class I histocompatibility antigen, A-126 alpha chain isoform X1 [KO:K06751 ]
116272574 patr class I histocompatibility antigen, A-126 alpha chain isoform X1 [KO:K06751 ]
100997583 HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751 ]
116272784 class I histocompatibility antigen, Gogo-B*0101 alpha chain-like isoform X1 [KO:K06751 ]
101022333 class I histocompatibility antigen, Gogo-B*0101 alpha chain-like isoform X1 [KO:K06751 ]
101003522 HLA class I histocompatibility antigen, B-27 alpha chain-like [KO:K06751 ]
101021633 HLA class I histocompatibility antigen, B-7 alpha chain-like [KO:K06751 ]
101006198 class I histocompatibility antigen, Gogo-B*0101 alpha chain [KO:K06751 ]
116268677 class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751 ]
116272937 HLA class I histocompatibility antigen, Cw-6 alpha chain-like isoform X1 [KO:K06751 ]
101012738 LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q9 alpha chain [KO:K06751 ]
101026217 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, B-27 alpha chain-like [KO:K06751 ]
101002482 class I histocompatibility antigen, Gogo-B*0101 alpha chain-like isoform X2 [KO:K06751 ]
116273056 HLA class I histocompatibility antigen, Cw-8 alpha chain-like isoform X1 [KO:K06751 ]
116273133 HLA class I histocompatibility antigen, B-67 alpha chain-like [KO:K06751 ]
116273134 HLA class I histocompatibility antigen, B-7 alpha chain-like [KO:K06751 ]
101020363 HLA class I histocompatibility antigen, B-67 alpha chain [KO:K06751 ]
101021052 HLA class I histocompatibility antigen, B-67 alpha chain [KO:K06751 ]
101024059 LOW QUALITY PROTEIN: patr class I histocompatibility antigen, alpha chain E [KO:K06751 ]
101015220 LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A-11 alpha chain [KO:K06751 ]
101009503 popy class I histocompatibility antigen, alpha chain E isoform X1 [KO:K06751 ]
100126713 PACA-F; major histocompatibility complex, class I, F precursor [KO:K06751 ]
101007932 patr class I histocompatibility antigen, A-126 alpha chain-like precursor [KO:K06751 ]
101006392 LOW QUALITY PROTEIN: uncharacterized protein LOC101006392 [KO:K10785 ]
101000210 FASLG; 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
KO pathway
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