KEGG   PATHWAY: pps04940
Entry
pps04940                    Pathway                                
Name
Type I diabetes mellitus - Pan paniscus (bonobo)
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
pps04940  Type I diabetes mellitus
pps04940

Disease
H00408  Type 1 diabetes mellitus
Organism
Pan paniscus (bonobo) [GN:pps]
Gene
100967723  [KO:K06752]
100967832  CD80; T-lymphocyte activation antigen CD80 [KO:K05412]
100968410  MHC-DMB; HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
100968828  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X1 [KO:K07817] [EC:3.1.3.48]
100968989  [KO:K06752]
100969387  INS; insulin [KO:K04526]
100970360  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100970847  [KO:K06752]
100972641  [KO:K06752]
100972994  [KO:K06752]
100973583  [KO:K06752]
100975263  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
100975678  [KO:K04077] [EC:5.6.1.7]
100977055  [KO:K06751]
100977674  TNF; tumor necrosis factor [KO:K03156]
100978112  Papa-A; patr class I histocompatibility antigen, A-2 alpha chain-like precursor [KO:K06751]
100978457  [KO:K06751]
100978473  PTPRN2; receptor-type tyrosine-protein phosphatase N2 isoform X1 [KO:K07817] [EC:3.1.3.48]
100978774  [KO:K06751]
100979338  [KO:K06751]
100979574  IL12A; interleukin-12 subunit alpha [KO:K05406]
100979649  [KO:K06752]
100979698  PRF1; perforin-1 isoform X2 [KO:K07818]
100979816  LTA; lymphotoxin-alpha [KO:K05468]
100979991  ICA1; islet cell autoantigen 1 isoform X5 [KO:K19863]
100981251  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
100981698  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
100982294  [KO:K06751]
100982859  [KO:K06751]
100983801  CPE; carboxypeptidase E isoform X1 [KO:K01294] [EC:3.4.17.10]
100984780  IL2; interleukin-2 [KO:K05429]
100986750  [KO:K06752]
100987081  [KO:K06752]
100987153  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
100988526  FAS; tumor necrosis factor receptor superfamily member 6 isoform X3 [KO:K04390]
100989950  IL12B; interleukin-12 subunit beta [KO:K05425]
100991779  IFNG; interferon gamma [KO:K04687]
100992093  CD28; T-cell-specific surface glycoprotein CD28 isoform X2 [KO:K06470]
100992436  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
100993452  [KO:K06751]
100993613  IL1B; interleukin-1 beta [KO:K04519]
100994286  IL1A; interleukin-1 alpha [KO:K04383]
100995226  [KO:K06752]
100995577  [KO:K06752]
134730587  [KO:K06752]
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
pps04210  Apoptosis
pps04660  T cell receptor signaling pathway
KO pathway
ko04940   

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