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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.
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Human Diseases; Endocrine and metabolic disease
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Pathway map |

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Disease |
H00408 | Type 1 diabetes mellitus |
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Rabinovitch A, Suarez-Pinzon WL. |
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Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. |
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Cox NJ, Wapelhorst B, Morrison VA, Johnson L, Pinchuk L, Spielman RS, Todd JA, Concannon P |
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Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families. |
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Davies JL, Kawaguchi Y, Bennett ST, Copeman JB, Cordell HJ, Pritchard LE, Reed PW, Gough SC, Jenkins SC, Palmer SM, et al. |
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A genome-wide search for human type 1 diabetes susceptibility genes. |
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Authors |
Fujisawa T, Ikegami H, Kawaguchi Y, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Ueda H, Shima K, Ogihara T. |
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Class I HLA is associated with age-at-onset of IDDM, while class II HLA confers susceptibility to IDDM. |
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Jaeckel E, Klein L, Martin-Orozco N, von Boehmer H. |
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Normal incidence of diabetes in NOD mice tolerant to glutamic acid decarboxylase. |
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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. |
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Authors |
Kent SC, Chen Y, Bregoli L, Clemmings SM, Kenyon NS, Ricordi C, Hering BJ, Hafler DA. |
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Expanded T cells from pancreatic lymph nodes of type 1 diabetic subjects recognize an insulin epitope. |
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Authors |
Lieberman SM, DiLorenzo TP. |
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A comprehensive guide to antibody and T-cell responses in type 1 diabetes. |
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Authors |
Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC. |
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Granzyme B: a natural born killer. |
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Related pathway |
map04660 | T cell receptor signaling pathway |
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KO pathway |
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