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Enterovirus infection of human islets of Langerhans affects β-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

Hodik, M., Skog, O., Lukinius, A., Isaza-Correa, J. M., Kuipers, J., Giepmans, B. N. G. & Frisk, G., Aug-2016, In : BMJ Open Diabetes Research & Care. 4, 1, 10 p., e000179.

Research output: Contribution to journalArticleAcademicpeer-review

AIMS/HYPOTHESIS: In type 1 diabetes (T1D), most insulin-producing β cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion.

METHODS: Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected β cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes.

RESULTS: In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected β cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in β cells. There was a significant number of insulin granules remaining in the virus-infected β cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion.

CONCLUSIONS/INTERPRETATION: Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in β cells.

Original languageEnglish
Article numbere000179
Number of pages10
JournalBMJ Open Diabetes Research & Care
Volume4
Issue number1
Publication statusPublished - Aug-2016

    Keywords

  • Journal Article, DOUBLE-STRANDED-RNA, COMPLETE NUCLEOTIDE-SEQUENCE, COXSACKIE B4 VIRUS, DIABETES-MELLITUS, RECENT-ONSET, VIRAL-RNA, IN-VITRO, PANCREATIC-ISLETS, MOUSE ISLETS, NITRIC-OXIDE

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