New research conducted in mice has shown how coxsackievirus B type 4 can cause diabetes in individuals who have the virus, an enterovirus, a virus transmitted via the intestines.
A recent research has shown that people who have coxsackievirus B type 4 (CVB4), a type of enterovirus, have a potential mechanism for causing diabetes.
The research, reported in the journal Cell Reports Medicine, may also be useful in investigating whether diabetes may be caused by SARS-CoV-2, the virus at the heart of the current pandemic.
Diabetes
Diabetes is an ongoing health disorder that affects how a person’s body converts food into energy, according to the Centers for Disease Control and Prevention ( CDC).
Their blood sugar rises as a person consumes food and drinks. Their pancreas then releases the insulin hormone, which helps cells to reach this sugar in the blood.
An individual with diabetes may not, however, be able to either make good use of or produce enough insulin (type 2 diabetes) (type 1 diabetes).
Type 2 diabetes is by far the most prevalent form of diabetes, accounting for around 90-95% of all diabetes cases in the adult population.
Both forms of diabetes are considered by the American Diabetes Association to be caused by a combination of genetic and environmental factors.
For type 1 diabetes, researchers assume that one aspect of these environmental variables is viruses.
In particular, study indicates that enteroviruses could be key viral causes for type 1 diabetes, a family of viruses that can cause a number of diseases with “neurological, respiratory, skin, and gastrointestinal” symptoms.
Scientists are not yet sure, however, exactly how this triggering function occurs.
Complex chain of events
The researchers wanted to better understand how enteroviruses can cause type 1 diabetes in the current study.
They used mice that had been grafted with CVB4 human pancreatic cells, as well as insulin-producing human and mouse cells that still had the virus, to do so.
The researchers identified a complex sequence of events that could account for the cause of diabetes after performing different experiments with these infected cells.
The researchers observed that infection with CVB4 induced downregulation of URI, a protein that regulates different function of the cell. This downregulation triggered a cascade of molecular events.
In turn, this resulted in the silencing of the Pdx1 gene, which regulates the pancreatic role of beta cells. Insulin is formed by these beta cells.
As explained by Dr. Nabil Djouder, a researcher at the Spanish National Cancer Research Center and lead author of the study, “Silencing Pdx1 triggers the loss of the identity and function of beta cells, which become more like alpha cells, responsible for raising blood glucose levels and thus leading to hyperglycemia and eventual diabetes, regardless of any immune reactions.”
The researchers also noted that mice with diabetes that overexpressed the URI protein were more tolerant of blood sugar changes to further corroborate their results.
Finally , the researchers noted a correlation between the expression of URI, Pdx1, and viral particles in pancreata from diabetes patients. For scientists, this indicates that human diabetes and enteroviruses have a causal link.
A prevention strategy?
In addition to helping to make clear the mechanism behind the viral triggering of diabetes, the research also increases the prospect of using antiviral therapies to prevent and treat diabetes alongside medicines that inhibit the silencing of Pdx1.
The researchers showed that Pdx1 expression and glucose tolerance in diabetic mice were restored by DNA methyltransferase inhibitors which inhibit a protein involved in the silencing of Pdx1.
The researchers claim their analysis may also have implications for the pandemic of COVID-19. “Similar to our research on enteroviruses, some recent clinical observations have related SARS-CoV-2, the virus responsible for COVID-19, to diabetes in infected patients,” Dr. Djouder explains.
“Since the receptor of SARS-CoV-2 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.”
– Dr. Nabil Djouder
