KEGG   PATHWAY: lcat04940
Entry
lcat04940                   Pathway                                
Name
Type I diabetes mellitus - Lemur catta (Ring-tailed lemur)
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
lcat04940  Type I diabetes mellitus
lcat04940

Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123642915  INS; insulin [KO:K04526]
123621729  glutamate decarboxylase 1-like [KO:K01580] [EC:4.1.1.15]
123626227  GAD2; glutamate decarboxylase 2 [KO:K01580] [EC:4.1.1.15]
123643976  PTPRN; LOW QUALITY PROTEIN: receptor-type tyrosine-protein phosphatase-like N [KO:K07817] [EC:3.1.3.48]
123638712  CPE; carboxypeptidase E [KO:K01294] [EC:3.4.17.10]
123643337  HSPD1; 60 kDa heat shock protein, mitochondrial [KO:K04077] [EC:5.6.1.7]
123647431  ICA1; islet cell autoantigen 1 isoform X1 [KO:K19863]
123631796  mamu class II histocompatibility antigen, DR alpha chain [KO:K06752]
123631797  HLA class II histocompatibility antigen, DRB1 beta chain-like [KO:K06752]
123631798  HLA class II histocompatibility antigen, DQ alpha 2 chain [KO:K06752]
123631799  HLA class II histocompatibility antigen, DQ beta 1 chain-like [KO:K06752]
123631804  HLA class II histocompatibility antigen, DO beta chain isoform X1 [KO:K06752]
123631807  HLA class II histocompatibility antigen, DM beta chain [KO:K06752]
123631808  HLA class II histocompatibility antigen, DM alpha chain isoform X1 [KO:K06752]
123631809  HLA class II histocompatibility antigen, DO alpha chain isoform X1 [KO:K06752]
123631812  HLA class II histocompatibility antigen, DP alpha 1 chain isoform X1 [KO:K06752]
123631813  HLA class II histocompatibility antigen, DP beta 1 chain-like isoform X1 [KO:K06752]
123631814  HLA class II histocompatibility antigen, DP beta 1 chain [KO:K06752]
123630513  CD80; T-lymphocyte activation antigen CD80 isoform X1 [KO:K05412]
123630490  CD86; T-lymphocyte activation antigen CD86 isoform X1 [KO:K05413]
123643862  CD28; T-cell-specific surface glycoprotein CD28 isoform X1 [KO:K06470]
123646097  IL12A; interleukin-12 subunit alpha [KO:K05406]
123638007  IL12B; interleukin-12 subunit beta [KO:K05425]
123637712  IL2; interleukin-2 [KO:K05429]
123640661  IFNG; interferon gamma [KO:K04687]
123631673  class I histocompatibility antigen, Gogo-B*0102 alpha chain-like isoform X1 [KO:K06751]
123631675  patr class I histocompatibility antigen, B-2 alpha chain-like isoform X1 [KO:K06751]
123631677  patr class I histocompatibility antigen, A-2 alpha chain-like [KO:K06751]
123631716  HLA class I histocompatibility antigen, alpha chain G-like isoform X1 [KO:K06751]
123634668  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
123649928  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
123649945  PRF1; perforin-1 [KO:K07818]
123650592  LOW QUALITY PROTEIN: granzyme B-like [KO:K01353] [EC:3.4.21.79]
123631723  LTA; lymphotoxin-alpha [KO:K05468]
123631724  TNF; tumor necrosis factor [KO:K03156]
123636470  IL1A; interleukin-1 alpha [KO:K04383]
123637166  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
lcat04210  Apoptosis
lcat04660  T cell receptor signaling pathway
KO pathway
ko04940   
LinkDB

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