KEGG   PATHWAY: bacu04940
Entry
bacu04940                   Pathway                                
Name
Type I diabetes mellitus - Balaenoptera acutorostrata scammoni (minke whale)
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
bacu04940  Type I diabetes mellitus
bacu04940

Organism
Balaenoptera acutorostrata scammoni (minke whale) [GN:bacu]
Gene
103021022  INS; insulin [KO:K04526]
102997733  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
103010874  GAD1; glutamate decarboxylase 1 [KO:K01580] [EC:4.1.1.15]
102999559  PTPRN2; protein tyrosine phosphatase, receptor type N2 [KO:K07817] [EC:3.1.3.48]
103008376  PTPRN; protein tyrosine phosphatase, receptor type N [KO:K07817] [EC:3.1.3.48]
103006962  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
103016205  HSPD1; heat shock protein family D (Hsp60) member 1 [KO:K04077] [EC:5.6.1.7]
103004565  ICA1; islet cell autoantigen 1 [KO:K19863]
103008197  HLA class II histocompatibility antigen, DO alpha chain-like [KO:K06752]
103009822  HLA class II histocompatibility antigen, DM alpha chain-like [KO:K06752]
103010705  HLA class II histocompatibility antigen, DM beta chain-like [KO:K06752]
103012629  HLA class II histocompatibility antigen, DO beta chain-like [KO:K06752]
103007535  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
103007833  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
103007035  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
103003018  CD80; CD80 molecule [KO:K05412]
102998972  CD86; CD86 molecule [KO:K05413]
103017404  CD28; CD28 molecule [KO:K06470]
103003516  IL12A; interleukin 12A [KO:K05406]
103007028  IL12B; interleukin 12B [KO:K05425]
103017896  IL2; interleukin 2 [KO:K05429]
103020304  IFNG; interferon gamma [KO:K04687]
103008230  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
103007740  BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
103003614  uncharacterized LOC103003614 [KO:K10785]
102999836  FASLG; Fas ligand [KO:K04389]
103020508  FAS; Fas cell surface death receptor [KO:K04390]
103015146  PRF1; perforin 1 [KO:K07818]
103000247  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
103010961  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
103006180  LTA; lymphotoxin alpha [KO:K05468]
103005897  TNF; tumor necrosis factor [KO:K03156]
103008155  IL1A; interleukin 1 alpha [KO:K04383]
103008438  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
bacu04210  Apoptosis
bacu04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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