KEGG   PATHWAY: pyu04940
Entry
pyu04940                    Pathway                                
Name
Type I diabetes mellitus - Puma yagouaroundi (jaguarundi)
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
pyu04940  Type I diabetes mellitus
pyu04940

Organism
Puma yagouaroundi (jaguarundi) [GN:pyu]
Gene
121023965  INS; insulin [KO:K04526]
121030684  GAD1; glutamate decarboxylase 1 isoform X1 [KO:K01580] [EC:4.1.1.15]
121032693  LOW QUALITY PROTEIN: glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
121014696  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
121031107  PTPRN; receptor-type tyrosine-protein phosphatase-like N isoform X1 [KO:K07817] [EC:3.1.3.48]
121022982  PTPRN2; receptor-type tyrosine-protein phosphatase N2 [KO:K07817] [EC:3.1.3.48]
121027536  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
121030872  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
121016991  60 kDa heat shock protein, mitochondrial-like [KO:K04077] [EC:5.6.1.7]
121028684  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
121021858  HLA class II histocompatibility antigen, DR alpha chain [KO:K06752]
121023070  HLA class II histocompatibility antigen, DR alpha chain-like [KO:K06752]
121026708  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
121026710  HLA class II histocompatibility antigen, DR beta 5 chain-like [KO:K06752]
121026711  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
121029254  DLA class II histocompatibility antigen, DR-1 beta chain-like [KO:K06752]
121029256  HLA class II histocompatibility antigen, DO beta chain-like isoform X1 [KO:K06752]
121029263  HLA class II histocompatibility antigen, DM beta chain isoform X1 [KO:K06752]
121029264  HLA class II histocompatibility antigen, DM alpha chain [KO:K06752]
121029266  HLA class II histocompatibility antigen, DO alpha chain [KO:K06752]
121029268  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
121029269  LOW QUALITY PROTEIN: HLA class II histocompatibility antigen, DP alpha 1 chain [KO:K06752]
121036277  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
121036316  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
121030946  CD28; T-cell-specific surface glycoprotein CD28 [KO:K06470]
121033922  IL12A; interleukin-12 subunit alpha isoform X1 [KO:K05406]
121010131  IL12B; interleukin-12 subunit beta isoform X1 [KO:K05425]
121030128  IL2; interleukin-2 [KO:K05429]
121041076  IFNG; interferon gamma [KO:K04687]
121022363  LOW QUALITY PROTEIN: patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
121023084  DLA class I histocompatibility antigen, A9/A9 alpha chain-like isoform X1 [KO:K06751]
121023085  class I histocompatibility antigen, Gogo-C*0203 alpha chain-like isoform X1 [KO:K06751]
121023100  LOW QUALITY PROTEIN: BOLA class I histocompatibility antigen, alpha chain BL3-7-like [KO:K06751]
121023114  class I histocompatibility antigen, Gogo-B*0101 alpha chain-like isoform X1 [KO:K06751]
121023115  LOW QUALITY PROTEIN: DLA class I histocompatibility antigen, A9/A9 alpha chain-like [KO:K06751]
121024246  class I histocompatibility antigen, Gogo-B*0201 alpha chain-like isoform X1 [KO:K06751]
121024278  class I histocompatibility antigen, Gogo-B*0201 alpha chain-like [KO:K06751]
121016637  H-2 class I histocompatibility antigen, Q10 alpha chain-like isoform X1 [KO:K06751]
121031448  uncharacterized protein LOC121031448 [KO:K10784]
121028976  M1-specific T cell receptor beta chain-like [KO:K10785]
121015025  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
121016588  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
121036746  PRF1; perforin-1 isoform X1 [KO:K07818]
121031586  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
121031587  granzyme B-like [KO:K01353] [EC:3.4.21.79]
121022313  LTA; lymphotoxin-alpha [KO:K05468]
121022312  TNF; tumor necrosis factor [KO:K03156]
121044461  IL1A; interleukin-1 alpha isoform X1 [KO:K04383]
121044460  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
pyu04210  Apoptosis
pyu04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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