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dc.contributor.authorGallagher, Glen R.
dc.contributor.authorBrehm, Michael A.
dc.contributor.authorFinberg, Robert W.
dc.contributor.authorBarton, Bruce A.
dc.contributor.authorShultz, Leonard D.
dc.contributor.authorGreiner, Dale L.
dc.contributor.authorBortell, Rita
dc.contributor.authorWang, Jennifer P.
dc.date2022-08-11T08:08:55.000
dc.date.accessioned2022-08-23T16:12:17Z
dc.date.available2022-08-23T16:12:17Z
dc.date.issued2015-04-01
dc.date.submitted2015-08-13
dc.identifier.citationDiabetes. 2015 Apr;64(4):1358-69. doi: 10.2337/db14-1020. Epub 2014 Nov 12. <a href="http://dx.doi.org/10.2337/db14-1020">Link to article on publisher's site</a>
dc.identifier.issn0012-1797 (Linking)
dc.identifier.doi10.2337/db14-1020
dc.identifier.pmid25392246
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33363
dc.description.abstractType 1 diabetes (T1D) is characterized by the destruction of the insulin-producing beta-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native beta-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of beta-cells, resulting in diabetes. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25392246&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.2337/db14-1020
dc.subjectAnimals; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Enterovirus B, Human; Humans; Hyperglycemia; Islets of Langerhans; *Islets of Langerhans Transplantation; Mice
dc.subjectEndocrine System
dc.subjectEndocrine System Diseases
dc.subjectImmunology and Infectious Disease
dc.subjectMolecular Genetics
dc.titleViral infection of engrafted human islets leads to diabetes
dc.typeJournal Article
dc.source.journaltitleDiabetes
dc.source.volume64
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1888
dc.identifier.contextkey7457243
html.description.abstract<p>Type 1 diabetes (T1D) is characterized by the destruction of the insulin-producing beta-cells of pancreatic islets. Genetic and environmental factors both contribute to T1D development. Viral infection with enteroviruses is a suspected trigger for T1D, but a causal role remains unproven and controversial. Studies in animals are problematic because of species-specific differences in host cell susceptibility and immune responses to candidate viral pathogens such as coxsackievirus B (CVB). In order to resolve the controversial role of viruses in human T1D, we developed a viral infection model in immunodeficient mice bearing human islet grafts. Hyperglycemia was induced in mice by specific ablation of native beta-cells. Human islets, which are naturally susceptible to CVB infection, were transplanted to restore normoglycemia. Transplanted mice were infected with CVB4 and monitored for hyperglycemia. Forty-seven percent of CVB4-infected mice developed hyperglycemia. Human islet grafts from infected mice contained viral RNA, expressed viral protein, and had reduced insulin levels compared with grafts from uninfected mice. Human-specific gene expression profiles in grafts from infected mice revealed the induction of multiple interferon-stimulated genes. Thus, human islets can become severely dysfunctional with diminished insulin production after CVB infection of beta-cells, resulting in diabetes. long as the work is properly cited, the use is educational and not for profit, and the work is not altered.</p>
dc.identifier.submissionpathgsbs_sp/1888
dc.contributor.departmentDepartment of Quantitative Health Sciences
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Medicine
dc.source.pages1358-69
dc.contributor.studentGlen Gallagher


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