KEGG   PATHWAY: myb04940
Entry
myb04940                    Pathway                                
Name
Type I diabetes mellitus - Myotis brandtii (Brandt's bat)
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
myb04940  Type I diabetes mellitus
myb04940

Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102254396  insulin [KO:K04526]
102241538  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
102255123  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
102260866  PTPRN2; protein tyrosine phosphatase, receptor type N2 [KO:K07817] [EC:3.1.3.48]
102262356  PTPRN; protein tyrosine phosphatase, receptor type N [KO:K07817] [EC:3.1.3.48]
102263369  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
102253603  HSPD1; heat shock protein family D (Hsp60) member 1 [KO:K04077] [EC:5.6.1.7]
102255440  60 kDa heat shock protein, mitochondrial-like [KO:K04077] [EC:5.6.1.7]
102249453  ICA1; islet cell autoantigen 1 [KO:K19863]
102252603  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
102242640  H-2 class II histocompatibility antigen, E-S beta chain [KO:K06752]
102241033  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102241645  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102242559  HLA class II histocompatibility antigen, DRB1-1 beta chain [KO:K06752]
102242249  HLA class II histocompatibility antigen, DRB1-4 beta chain [KO:K06752]
102263678  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102255852  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102256158  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102251097  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
102250801  HLA class II histocompatibility antigen, DQ beta 1 chain [KO:K06752]
102242568  SLA class II histocompatibility antigen, DQ haplotype D beta chain [KO:K06752]
102242876  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102259226  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
102249039  H-2 class II histocompatibility antigen, A-U alpha chain [KO:K06752]
102263829  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
102245034  DLA class II histocompatibility antigen, DR-1 beta chain [KO:K06752]
102259410  HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
102249578  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
102252319  RLA class II histocompatibility antigen, DP alpha-1 chain-like [KO:K06752]
102251129  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
102251414  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
102244632  SLA class II histocompatibility antigen, DQ haplotype C beta chain-like [KO:K06752]
102245825  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
102246131  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
102263238  CD80; CD80 molecule [KO:K05412]
102256413  CD86; CD86 molecule [KO:K05413]
102239113  CD28; CD28 molecule [KO:K06470]
102251395  IL12A; interleukin 12A [KO:K05406]
102253394  IL12B; interleukin 12B [KO:K05425]
102246940  IL2; interleukin 2 [KO:K05429]
102254028  IFNG; interferon gamma [KO:K04687]
102249981  saoe class I histocompatibility antigen, A alpha chain [KO:K06751]
102252287  HLA class I histocompatibility antigen, B-15 alpha chain [KO:K06751]
102244169  HLA class I histocompatibility antigen, B-73 alpha chain [KO:K06751]
102261511  patr class I histocompatibility antigen, B-2 alpha chain [KO:K06751]
102241517  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
102251204  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
102254895  H-2 class I histocompatibility antigen, alpha chain-like [KO:K06751]
102258682  HLA class I histocompatibility antigen, B-14 alpha chain [KO:K06751]
102260771  patr class I histocompatibility antigen, B-2 alpha chain [KO:K06751]
102252800  class I histocompatibility antigen, Gogo-B*0103 alpha chain [KO:K06751]
102247150  patr class I histocompatibility antigen, B-2 alpha chain-like [KO:K06751]
102241975  class I histocompatibility antigen, Gogo-OKO alpha chain [KO:K06751]
102250885  HLA class I histocompatibility antigen, B-82 alpha chain-like [KO:K06751]
102256169  patr class I histocompatibility antigen, B-2 alpha chain-like [KO:K06751]
102257066  saoe class I histocompatibility antigen, A alpha chain-like [KO:K06751]
102257425  HLA class I histocompatibility antigen, B-7 alpha chain [KO:K06751]
102254369  HLA class I histocompatibility antigen, alpha chain E-like [KO:K06751]
102262076  FASLG; Fas ligand [KO:K04389]
102259838  FAS; Fas cell surface death receptor [KO:K04390]
102241005  PRF1; perforin 1 [KO:K07818]
102255120  granzyme B [KO:K01353] [EC:3.4.21.79]
102256937  granzyme B [KO:K01353] [EC:3.4.21.79]
102255724  GZMH; granzyme H [KO:K01353] [EC:3.4.21.79]
102254077  granzyme B-like [KO:K01353] [EC:3.4.21.79]
102254375  granzyme H-like [KO:K01353] [EC:3.4.21.79]
102261579  granzyme B [KO:K01353] [EC:3.4.21.79]
102247784  LTA; lymphotoxin alpha [KO:K05468]
102246703  TNF; tumor necrosis factor [KO:K03156]
102251877  IL1A; interleukin 1 alpha [KO:K04383]
102251576  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
PMID:11507694
  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
PMID:12796471
  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
PMID:15889095
  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
PMID:15889096
  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
PMID:14617043
  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
PMID:12752668
  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
myb04210  Apoptosis
myb04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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