KEGG   PATHWAY: gas04940
Entry
gas04940                    Pathway                                
Name
Type I diabetes mellitus - Gracilinanus agilis (agile gracile opossum)
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
gas04940  Type I diabetes mellitus
gas04940

Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123256044  INS; insulin [KO:K04526]
123249218  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
123239259  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
123252966  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
123249851  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
123240159  PTPRN; receptor-type tyrosine-protein phosphatase-like N [KO:K07817] [EC:3.1.3.48]
123251233  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
123242140  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
123249307  ICA1; islet cell autoantigen 1 [KO:K19863]
123256290  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR beta 4 chain-like [KO:K06752]
123245189  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
123245190  mamu class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
123245191  H-2 class II histocompatibility antigen, A-U alpha chain-like [KO:K06752]
123245192  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
123245340  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
123245626  H-2 class II histocompatibility antigen, E-S beta chain-like isoform X1 [KO:K06752]
123245629  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
123246365  H-2 class II histocompatibility antigen, A-R alpha chain-like [KO:K06752]
123246408  LOW QUALITY PROTEIN: DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
123246413  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
123246951  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
123241555  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
123241544  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
123241905  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
123242043  IL12A; interleukin-12 subunit alpha [KO:K05406]
123235575  IL12B; interleukin-12 subunit beta [KO:K05425]
123251137  IL2; interleukin-2 [KO:K05429]
123250180  IFNG; interferon gamma [KO:K04687]
123255734  LOW QUALITY PROTEIN: major histocompatibility complex class I-related gene protein-like [KO:K06751]
123243714  HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751]
123233108  hereditary hemochromatosis protein homolog [KO:K06751]
123233110  hereditary hemochromatosis protein homolog [KO:K06751]
123233132  zinc-alpha-2-glycoprotein-like [KO:K06751]
123233134  zinc-alpha-2-glycoprotein-like [KO:K06751]
123245212  class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751]
123245214  class I histocompatibility antigen, Gogo-OKO alpha chain-like [KO:K06751]
123245219  patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751]
123234493  zinc-alpha-2-glycoprotein-like [KO:K06751]
123234494  zinc-alpha-2-glycoprotein-like [KO:K06751]
123234496  class I histocompatibility antigen, F10 alpha chain-like [KO:K06751]
123246364  class I histocompatibility antigen, Gogo-B*0201 alpha chain-like [KO:K06751]
123233133  zinc-alpha-2-glycoprotein-like [KO:K06751]
123234499  zinc-alpha-2-glycoprotein-like [KO:K06751]
123253831  zinc-alpha-2-glycoprotein-like [KO:K06751]
123253834  zinc-alpha-2-glycoprotein-like [KO:K06751]
123245896  FASLG; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 6 [KO:K04389]
123236504  PRF1; perforin-1 [KO:K07818]
123235914  granzyme B-like [KO:K01353] [EC:3.4.21.79]
123245102  LTA; lymphotoxin-alpha [KO:K05468]
123245100  TNF; tumor necrosis factor [KO:K03156]
123236271  IL1A; interleukin-1 alpha [KO:K04383]
123234542  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
gas04210  Apoptosis
gas04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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