KEGG   PATHWAY: mbez04940
Entry
mbez04940                   Pathway                                
Name
Type I diabetes mellitus - Moschus berezovskii (Chinese forest musk deer)
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
mbez04940  Type I diabetes mellitus
mbez04940

Organism
Moschus berezovskii (Chinese forest musk deer) [GN:mbez]
Gene
129548407  INS; insulin [KO:K04526]
129549609  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
129538278  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
129555292  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
129537894  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X1 [KO:K07817] [EC:3.1.3.48]
129552818  PTPRN2; receptor-type tyrosine-protein phosphatase N2 isoform X1 [KO:K07817] [EC:3.1.3.48]
129542728  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
129538691  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
129552254  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
129543058  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
129543060  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
129543211  rano class II histocompatibility antigen, A beta chain-like [KO:K06752]
129543214  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
129543215  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543218  HLA class II histocompatibility antigen, DQ alpha 2 chain-like isoform X1 [KO:K06752]
129543236  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
129543392  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543470  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
129543574  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129543605  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129543630  boLa class II histocompatibility antigen, DQB*0101 beta chain [KO:K06752]
129543645  DLA class II histocompatibility antigen, DR-1 beta chain-like isoform X1 [KO:K06752]
129543651  HLA class II histocompatibility antigen, DO beta chain [KO:K06752]
129543663  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129557775  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129547512  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129547513  boLa class II histocompatibility antigen, DQB*0101 beta chain-like [KO:K06752]
129547514  SLA class II histocompatibility antigen, DQ haplotype D alpha chain-like [KO:K06752]
129560376  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
129534977  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
129537909  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
129551055  IL12A; interleukin-12 subunit alpha [KO:K05406]
129558692  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
129542297  IL2; interleukin-2 [KO:K05429]
129536468  IFNG; interferon gamma [KO:K04687]
129543112  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
129543113  BOLA class I histocompatibility antigen, alpha chain BL3-7 isoform X1 [KO:K06751]
129543114  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
129543175  BOLA class I histocompatibility antigen, alpha chain BL3-7-like isoform X1 [KO:K06751]
129543498  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
129558890  LOW QUALITY PROTEIN: H-2 class I histocompatibility antigen, Q10 alpha chain-like [KO:K06751]
129551094  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
129555563  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
129555080  PRF1; perforin-1 [KO:K07818]
129550080  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
129550130  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
129550131  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
129550478  granzyme B-like [KO:K01353] [EC:3.4.21.79]
129550480  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
129543582  LTA; lymphotoxin-alpha [KO:K05468]
129543262  TNF; tumor necrosis factor isoform X1 [KO:K03156]
129539790  IL1A; interleukin-1 alpha [KO:K04383]
129539906  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
mbez04210  Apoptosis
mbez04660  T cell receptor signaling pathway
KO pathway
ko04940   
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