Authors
Gallagher, Glen R.Brehm, Michael A.
Finberg, Robert W.
Barton, Bruce A.
Shultz, Leonard D.
Greiner, Dale L.
Bortell, Rita
Wang, Jennifer P.
Student Authors
Glen GallagherUMass Chan Affiliations
Department of Quantitative Health SciencesProgram in Molecular Medicine
Department of Medicine
Document Type
Journal ArticlePublication Date
2015-04-01Keywords
Animals; Coxsackievirus Infections; Diabetes Mellitus, Type 1; Enterovirus B, Human; Humans; Hyperglycemia; Islets of Langerhans; *Islets of Langerhans Transplantation; MiceEndocrine System
Endocrine System Diseases
Immunology and Infectious Disease
Molecular Genetics
Metadata
Show full item recordAbstract
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.Source
Diabetes. 2015 Apr;64(4):1358-69. doi: 10.2337/db14-1020. Epub 2014 Nov 12. Link to article on publisher's siteDOI
10.2337/db14-1020Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33363PubMed ID
25392246Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.2337/db14-1020