KEGG   PATHWAY: cdk04940
Entry
cdk04940                    Pathway                                
Name
Type I diabetes mellitus - Camelus dromedarius (Arabian camel)
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
cdk04940  Type I diabetes mellitus
cdk04940

Organism
Camelus dromedarius (Arabian camel) [GN:cdk]
Gene
116152037  INS; insulin [KO:K04526]
105089013  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
105091082  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
105102071  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
105096111  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X6 [KO:K07817] [EC:3.1.3.48]
105088983  PTPRN2; receptor-type tyrosine-protein phosphatase N2 isoform X1 [KO:K07817] [EC:3.1.3.48]
105089282  CPE; LOW QUALITY PROTEIN: carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
105088805  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
105088702  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
105101397  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
105101401  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
105101402  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
105101408  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
105101409  LOW QUALITY PROTEIN: SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
105101412  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
105101414  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
105101433  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
105101434  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
105101437  HLA class II histocompatibility antigen, DRB1-1 beta chain-like isoform X2 [KO:K06752]
105101410  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
116147669  LOW QUALITY PROTEIN: boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
105101411  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
116147670  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
105101413  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
105090327  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
105090303  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
105098982  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
105094260  IL12A; interleukin-12 subunit alpha isoform X2 [KO:K05406]
105099900  IL12B; interleukin-12 subunit beta [KO:K05425]
105093664  IL2; interleukin 2 precursor [KO:K05429]
105101111  IFNG; interferon gamma [KO:K04687]
105087509  BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X1 [KO:K06751]
105087478  patr class I histocompatibility antigen, B-1 alpha chain isoform X1 [KO:K06751]
105087511  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
116147754  LOW QUALITY PROTEIN: saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
105104206  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
116152169  class I histocompatibility antigen, Gogo-B*0201 alpha chain-like [KO:K06751]
105092770  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
105102832  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
105099893  PRF1; perforin-1 [KO:K07818]
105094200  granzyme B [KO:K01353] [EC:3.4.21.79]
116153492  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
116153371  granzyme B-like [KO:K01353] [EC:3.4.21.79]
105087474  LTA; lymphotoxin-alpha [KO:K05468]
105087473  TNF; tumor necrosis factor [KO:K03156]
105093151  IL1A; interleukin-1 alpha [KO:K04383]
105093155  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
cdk04210  Apoptosis
cdk04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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