KEGG   PATHWAY: cbai04940
Entry
cbai04940                   Pathway                                
Name
Type I diabetes mellitus - Camelus bactrianus (Bactrian camel)
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
cbai04940  Type I diabetes mellitus
cbai04940

Organism
Camelus bactrianus (Bactrian camel) [GN:cbai]
Gene
105076792  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
105073990  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
105065117  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
105075232  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
105064044  PTPRN; receptor-type tyrosine-protein phosphatase-like N [KO:K07817] [EC:3.1.3.48]
105079738  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
105082327  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
105082540  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
105064235  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
105064238  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
105064239  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
105064245  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
105064246  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
105064247  HLA class II histocompatibility antigen, DRB1-1 beta chain-like isoform X1 [KO:K06752]
105064248  SLA class II histocompatibility antigen, DQ haplotype D alpha chain [KO:K06752]
105064249  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
105064250  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
105064272  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
105064273  HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
105064275  LOW QUALITY PROTEIN: SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
105064276  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
105071695  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DRB1-4 beta chain-like [KO:K06752]
105081591  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
105081617  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
105082279  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
105066646  IL12A; interleukin-12 subunit alpha [KO:K05406]
105065241  IL12B; interleukin-12 subunit beta [KO:K05425]
105067115  IL2; interleukin-2 [KO:K05429]
105081344  IFNG; interferon gamma [KO:K04687]
105074080  HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751]
105074082  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
105074083  LOW QUALITY PROTEIN: histocompatibility antigen-related [KO:K06751]
105074084  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
105074117  saoe class I histocompatibility antigen, A alpha chain-like isoform X1 [KO:K06751]
105065248  HLA class I histocompatibility antigen, Cw-8 alpha chain-like [KO:K06751]
105061640  putative HLA class I histocompatibility antigen, alpha chain H [KO:K06751]
105070302  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
105081852  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
105066382  PRF1; perforin-1 [KO:K07818]
105075274  granzyme B-like [KO:K01353] [EC:3.4.21.79]
105068826  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
105074075  LTA; lymphotoxin-alpha [KO:K05468]
105074074  TNF; tumor necrosis factor [KO:K03156]
105072138  IL1A; interleukin-1 alpha [KO:K04383]
105072137  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
cbai04210  Apoptosis
cbai04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

DBGET integrated database retrieval system