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.
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.
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DOI：
10.1136/bmjdrc-2015-000179
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发表时间：
2016
影响因子：
4.1
通讯作者：
Frisk G
中科院分区：
文献类型：
--
作者：
Hodik M;Skog O;Lukinius A;Isaza-Correa JM;Kuipers J;Giepmans BN;Frisk G
在1型糖尿病(T1D)中，大多数产生胰岛素的β细胞被破坏，但触发因素尚不清楚。可能的触发因素之一是病毒感染，本研究的目的是测试肠道病毒感染是否影响葡萄糖刺激的胰岛素分泌，以及病毒复制对参与胰岛素分泌的细胞大分子和细胞器的影响。分离的人胰岛感染不同株的柯萨奇B组病毒(CVB)，在动态灌流系统中测定葡萄糖刺激的胰岛素释放(GSIS)。用经典的形态电子显微镜、大规模电子显微镜、所谓的纳米切片法和免疫组织化学方法研究病毒感染的β细胞含有胰岛素的程度，并用实时定量聚合酶链式反应分析病毒诱导的胰岛特异性基因的变化。在感染CVB的胰岛中，GSIS降低与病毒诱导的胰岛解体程度相关。感染的胰岛胰岛素编码基因表达降低，而胰升糖素的表达不受影响。此外，在有些解体的胰岛中，有未受感染的β细胞。超微结构分析表明，病毒颗粒和病毒复制复合体仅存在于β细胞中。在感染病毒的β细胞中，尽管胰岛素基因表达减少，但仍有大量的胰岛素颗粒残留。此外，在这些细胞中未检测到典型的高尔基体。将胰岛暴露于合成dsRNA可增强葡萄糖刺激的胰岛素分泌。β细胞中参与胰岛素分泌的细胞器和基因表达均受柯萨奇病毒复制的影响。
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. 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. 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. Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in β cells.