KEGG   PATHWAY: btax04940
Entry
btax04940                   Pathway                                
Name
Type I diabetes mellitus - Budorcas taxicolor (takin)
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
btax04940  Type I diabetes mellitus
btax04940

Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128069208  INS; insulin [KO:K04526]
128058460  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
128066935  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
128067378  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
128070442  PTPRN; receptor-type tyrosine-protein phosphatase-like N [KO:K07817] [EC:3.1.3.48]
128046367  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
128062434  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
128062057  HSPD1; 60 kDa heat shock protein, mitochondrial isoform X1 [KO:K04077] [EC:5.6.1.7]
128046425  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
128056359  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DQ alpha 2 chain-like [KO:K06752]
128056564  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
128056652  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
128056806  LOW QUALITY PROTEIN: rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
128056812  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
128055329  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
128055330  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
128055331  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
128055332  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
128055370  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
128055541  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
128055605  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
128055814  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
128056011  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
128057447  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
128052556  CD86; T-lymphocyte activation antigen CD86 [KO:K05413]
128060911  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
128050368  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
128051514  IL12B; interleukin-12 subunit beta [KO:K05425]
128062529  IL2; interleukin-2 [KO:K05429]
128048506  IFNG; interferon gamma [KO:K04687]
128050979  H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
128055236  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
128055280  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
128055281  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
128055305  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
128061812  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128067871  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128048835  PRF1; perforin-1 [KO:K07818]
128066475  mast cell protease 1A [KO:K01353] [EC:3.4.21.79]
128066549  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128066641  mast cell protease 3 [KO:K01353] [EC:3.4.21.79]
128066644  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128067007  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128067008  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128056921  LTA; lymphotoxin-alpha [KO:K05468]
128056772  TNF; tumor necrosis factor [KO:K03156]
128056679  IL1A; interleukin-1 alpha [KO:K04383]
128056569  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
btax04210  Apoptosis
btax04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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