KEGG   PATHWAY: nvs04940
Entry
nvs04940                    Pathway                                
Name
Type I diabetes mellitus - Neogale vison (American mink)
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
nvs04940  Type I diabetes mellitus
nvs04940

Organism
Neogale vison (American mink) [GN:nvs]
Gene
122914590  INS; insulin [KO:K04526]
122891635  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
122902581  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
122903565  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
122905483  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
122902338  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X1 [KO:K07817] [EC:3.1.3.48]
122889555  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
122890336  LOW QUALITY PROTEIN: 60 kDa heat shock protein, mitochondrial-like [KO:K04077] [EC:5.6.1.7]
122899546  LOW QUALITY PROTEIN: 60 kDa heat shock protein, mitochondrial-like [KO:K04077] [EC:5.6.1.7]
122902154  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
122904856  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
122904655  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
122904716  H-2 class II histocompatibility antigen, E-S beta chain-like [KO:K06752]
122911007  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X1 [KO:K06752]
122911034  RLA class II histocompatibility antigen, DP alpha-1 chain [KO:K06752]
122911086  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
122911149  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
122911160  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
122911197  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
122911212  HLA class II histocompatibility antigen, DQ beta 1 chain isoform X1 [KO:K06752]
122911237  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
122911244  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
122911252  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
122911259  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
122908533  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
122908886  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
122901713  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
122910459  IL12A; interleukin-12 subunit alpha [KO:K05406]
122901988  IL12B; interleukin-12 subunit beta [KO:K05425]
122890130  IL2; interleukin-2 [KO:K05429]
122891375  IFNG; interferon gamma [KO:K04687]
122911831  class I histocompatibility antigen, Gogo-B*0103 alpha chain-like [KO:K06751]
122911837  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
122911846  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
122911852  DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]
122911871  DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
122911891  HLA class I histocompatibility antigen, alpha chain G-like [KO:K06751]
122907014  LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, A alpha chain [KO:K06751]
122915401  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
122894561  uncharacterized protein LOC122894561 [KO:K10784]
122918121  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
122900656  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
122898912  PRF1; perforin-1 [KO:K07818]
122893137  granzyme B-like [KO:K01353] [EC:3.4.21.79]
122894512  LOW QUALITY PROTEIN: mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
122899956  LTA; lymphotoxin-alpha [KO:K05468]
122899945  TNF; tumor necrosis factor isoform X1 [KO:K03156]
122915761  IL1A; interleukin-1 alpha [KO:K04383]
122915760  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
nvs04210  Apoptosis
nvs04660  T cell receptor signaling pathway
KO pathway
ko04940   
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