KEGG   PATHWAY: pcoq04940
Entry
pcoq04940                   Pathway                                
Name
Type I diabetes mellitus - Propithecus coquereli (Coquerel's sifaka)
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
Pathway map
pcoq04940  Type I diabetes mellitus
pcoq04940

Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105816531  INS; insulin [KO:K04526]
105818759  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
105815588  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
105821399  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
105808792  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X1 [KO:K07817] [EC:3.1.3.48]
105820514  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
105808089  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
105812916  ICA1; islet cell autoantigen 1 [KO:K19863]
105824372  H-2 class II histocompatibility antigen, I-E beta chain-like [KO:K06752]
105824381  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
105824383  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
105824384  HLA class II histocompatibility antigen, DP beta 1 chain-like [KO:K06752]
105824385  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
105824386  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
105824388  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
105824389  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
105817835  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
105817913  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
105810148  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
105806381  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
105806444  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
105819099  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
105809128  IL12A; interleukin-12 subunit alpha [KO:K05406]
105810764  IL12B; interleukin-12 subunit beta [KO:K05425]
105815260  IL2; interleukin-2 [KO:K05429]
105808396  IFNG; interferon gamma [KO:K04687]
105817846  HLA class I histocompatibility antigen, B-8 alpha chain-like [KO:K06751]
105817910  HLA class I histocompatibility antigen, B-46 alpha chain-like [KO:K06751]
105817268  patr class I histocompatibility antigen, A-108 alpha chain-like [KO:K06751]
105817288  HLA class I histocompatibility antigen, B-14 alpha chain-like isoform X1 [KO:K06751]
105817290  patr class I histocompatibility antigen, A-126 alpha chain-like isoform X1 [KO:K06751]
105817294  HLA class I histocompatibility antigen, B-41 alpha chain-like [KO:K06751]
105814175  uncharacterized protein LOC105814175 [KO:K10784]
105821114  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
105822691  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
105821806  PRF1; perforin-1 [KO:K07818]
105812752  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
105817906  LTA; lymphotoxin-alpha [KO:K05468]
105817905  TNF; tumor necrosis factor isoform X1 [KO:K03156]
105820319  IL1A; interleukin-1 alpha [KO:K04383]
105820326  IL1B; interleukin-1 beta [KO:K04519]
Compound
C00027  Hydrogen peroxide
C00533  Nitric oxide
C00704  Superoxide
Reference
PMID:9719467
  Authors
Rabinovitch A, Suarez-Pinzon WL.
  Title
Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus.
  Journal
Biochem Pharmacol 55:1139-49 (1998)
DOI:10.1016/S0006-2952(97)00492-9
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
Am J Hum Genet 69:820-30 (2001)
DOI:10.1086/323501
Reference
PMID:8072542
  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
Nature 371:130-6 (1994)
DOI:10.1038/371130a0
Reference
PMID:8786033
  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
Diabetologia 38:1493-5 (1995)
DOI:10.1007/BF00400620
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
J Exp Med 197:1635-44 (2003)
DOI:10.1084/jem.20030215
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
Nature 435:220-3 (2005)
DOI:10.1038/nature03523
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
Nature 435:224-8 (2005)
DOI:10.1038/nature03625
Reference
  Authors
Lieberman SM, DiLorenzo TP.
  Title
A comprehensive guide to antibody and T-cell responses in type 1 diabetes.
  Journal
Tissue Antigens 62:359-77 (2003)
DOI:10.1034/j.1399-0039.2003.00152.x
Reference
  Authors
Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
  Title
Granzyme B: a natural born killer.
  Journal
Immunol Rev 193:31-8 (2003)
DOI:10.1034/j.1600-065X.2003.00044.x
Related
pathway
pcoq04210  Apoptosis
pcoq04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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