KEGG   PATHWAY: bbis04940
Entry
bbis04940                   Pathway                                
Name
Type I diabetes mellitus - Bison bison bison (American bison)
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
bbis04940  Type I diabetes mellitus
bbis04940

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104999281  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
105003017  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
104991366  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
104980584  PTPRN2; LOW QUALITY PROTEIN: receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
105003865  PTPRN; receptor-type tyrosine-protein phosphatase-like N [KO:K07817] [EC:3.1.3.48]
104987645  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
105003623  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
104988412  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
104992400  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
104992401  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
104992404  HLA class II histocompatibility antigen, DRB1-1 beta chain-like isoform X1 [KO:K06752]
104992405  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
104992406  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
104998661  HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
104994876  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
104994877  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like isoform X1 [KO:K06752]
104994878  rano class II histocompatibility antigen, A beta chain-like isoform X1 [KO:K06752]
104994880  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
104994886  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
104994887  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
104994891  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
104992477  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
104984499  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
105003680  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
104988502  IL12A; interleukin-12 subunit alpha [KO:K05406]
104999734  IL12B; interleukin-12 subunit beta [KO:K05425]
105003236  IL2; interleukin-2 [KO:K05429]
104989779  IFNG; interferon gamma [KO:K04687]
104985847  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
104993295  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]
104994538  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
104994546  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
104994573  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
104983766  LOW QUALITY PROTEIN: HLA class I histocompatibility antigen, B-37 alpha chain-like [KO:K06751]
104983816  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
104999482  LOW QUALITY PROTEIN: uncharacterized protein LOC104999482 [KO:K10785]
104983199  uncharacterized protein LOC104983199 [KO:K10785]
104995820  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104987521  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
104997473  PRF1; perforin-1 [KO:K07818]
104991008  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
104991009  duodenase-1 [KO:K01353] [EC:3.4.21.79]
104991014  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
104991016  granzyme B-like [KO:K01353] [EC:3.4.21.79]
104983773  LTA; lymphotoxin-alpha [KO:K05468]
104983770  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104984413  IL1A; interleukin-1 alpha [KO:K04383]
104984411  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
bbis04210  Apoptosis
bbis04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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