Possible Link Between Enterovirus Infection and Diabetes Observed

Scientists have shown how the enterovirus coxsackievirus type B4 (CVB4) could induce diabetes. The team from the Spanish National Cancer Research Center published their results in Cell Reports Medicine. 

With the aim of finding and describing these mechanisms, the researchers worked with animal models engrafted with human pancreatic cells infected by CVB4, as well as with human and mouse insulin-producing cells, also infected with this virus. They observed that CVB4 infection induces deregulation of URI, a protein that regulates the normal functions of numerous cellular activities. 

"In this case, URI downregulation triggers a cascade of molecular events leading to a modification of the genome via hypermethylation and silencing of Pdx1. This is a gene critical for the identity and the function of beta cells present in the endocrine pancreas, at the so-called Islets of Langerhans, and responsible for the production and secretion of insulin, a hormone that decreases blood glucose levels," explains Nabil Djouder, lead author of the study. "PDX1 silencing causes the loss of the identity and function of the beta cells, which become more like alpha cells, in charge of increasing blood glucose levels, and hence leading to hyperglycemia and subsequent diabetes, independently of any immune reactions,” he adds. 

The researchers demonstrated their findings by using various genetically engineered mouse models and genomic studies. They show that loss of URI in mouse pancreata alters beta cell identity and function, leading to diabetes. Furthermore, they observed that diabetic mice that overexpress URI in beta cells are more tolerant to glucose. Finally, they demonstrated in several pancreata from diabetic patients that expression of URI, PDX1, and viral particles correlates in beta cells, highlighting a causal link between enterovirus infection and diabetes in humans.

"Similarly to our investigations on enteroviruses, some recent clinical observations have associated SARS-CoV-2, the virus responsible for COVID-19, to diabetes in infected patients," explains Djouder. "Since the receptor of SARS-Co-V2 is present in beta cells, it would be interesting to study if this virus also alters URI function and silences the expression of PDX1 to affect beta-cell function, promoting diabetes," he concludes.