Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Novel Insights into the Molecular Mechanisms by which Enteroviruses Impair Insulin-Secretion  (#122)

Emma Svedin 1 , Olli Laitinen 1 , Lena Eliasson 2 , Malin Flodström Tullberg 1
  1. Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden
  2. Unit of islet cell exocytosis, Lund University, Lund, Sweden

Until recently it was believed that all beta cells are destroyed in patients who develop type 1 diabetes (T1D). Recent studies have however shown that insulin positive beta cells remain in many patients. This suggests that an inability to secrete stored insulin contributes to the failure to maintain glucose homeostasis. Enteroviruses belonging to the group B Coxsackieviruses (CVBs) are believed to contribute to the development of T1D. Enterovirus RNA and protein have been found in islets of some T1D patients and infection of beta cells with enteroviruses in vitro results in defective insulin secretion. Enteroviruses express proteins that are required for virus replication. In addition, some of these proteins affect cellular functions in favour of virus propagation. This study aimed to investigate mechanisms by which CVBs cause beta cell dysfunction by testing the novel hypothesis that virus-encoded proteins affect insulin secretion. We first confirmed that CVB infected insulin producing cells demonstrate an impaired ability to secrete insulin in response to glucose. More importantly, we next showed that cells modified to express selected virus proteins had striking impairments in insulin secretion and that this could be attributed to effects on specific steps in the hormone secretion pathway

Our study confirms that enteroviruses impair beta cell function. Moreover, it demonstrates for the first time that this effect may be attributed to virus-encoded proteins. Our data provides a better understanding of how enteroviruses affect beta cell function. This information contributes to explain how viruses may be involved in T1D development and may provide the base for development of novel therapies aimed at preserving beta cell function.