| Molecular mimicry between insulin and retroviral antigen p73. Development of cross-reactive autoantibodies in sera of NOD and C57BL/KsJ db/db mice. | |
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MedLine Citation:
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PMID: 3286334 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enzyme-linked immunosorbent assay (ELISA) was used to study temporal development of murine autoantibodies against insulin and both type C and intracisternal type A retroviral antigens. The nonobese diabetic (NOD) mouse, a model for autoimmune, insulin-dependent diabetes, was compared with a related, but diabetes-resistant, strain, nonobese normal (NON). Similarly, C57BL/KsJ db/db mice (insulin-resistant model of insulin-dependent diabetes and obesity) were compared with diabetes-resistant C57BL/6 db/db mice. NOD mice developed much higher autoantibody titers than did NON mice. Whereas type C autoantibodies in NOD developed to peak titer shortly after mice were weaned, autoantibodies against insulin and p73 (group-specific antigen of the intracisternal type A particle) did not develop until shortly before, or concomitant with, the development of hyperglycemia. Two NOD mice not developing hyperglycemia during the 40-wk study period were distinguished from the mice developing diabetes by a delayed onset of insulin (but not p73) autoantibodies. Our findings suggest that in NOD mice, the appearance of insulin and p73 autoantibodies signifies that extensive underlying necrosis of beta-cells occurred. C57BL/KsJ db/db mice (with extensive beta-cell necrosis and early hyperglycemia) developed much higher autoantibody titers to insulin and p73 than did the diabetes-resistant C57BL/6 db/db mice. However, the presence of autoantibodies in normoglycemic C57BL/KsJ +/db controls demonstrated that elevated autoantibody titers alone were insufficient to produce diabetes in this model. Absorption studies indicated that autoantibodies against p73 recognized a common epitope on insulin and IgE-binding factor. The potential significance of this molecular mimicry is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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D V Serreze; E H Leiter; E L Kuff; P Jardieu; K Ishizaka |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Diabetes Volume: 37 ISSN: 0012-1797 ISO Abbreviation: Diabetes Publication Date: 1988 Mar |
Date Detail:
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Created Date: 1988-07-14 Completed Date: 1988-07-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 351-8 Citation Subset: AIM; IM |
Affiliation:
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Jackson Laboratory, Bar Harbor, ME 04609. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging Animals Antibody Formation Antigens, Viral / immunology* Autoantibodies / analysis* Cross Reactions Diabetes Mellitus, Experimental / immunology* Disease Models, Animal Enzyme-Linked Immunosorbent Assay Female Gene Products, gag Immunoglobulin G / analysis Immunoglobulin M / analysis Insulin / immunology* Lymphokines / immunology Male Mice Mice, Inbred C57BL Mice, Mutant Strains Prostatic Secretory Proteins* Retroviridae Proteins / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Viral; 0/Autoantibodies; 0/Gene Products, gag; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Lymphokines; 0/Prostatic Secretory Proteins; 0/Retroviridae Proteins; 0/beta-microseminoprotein; 0/immunoglobulin-binding factors; 11061-68-0/Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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