New research conducted in mice has shown how coxsackievirus B type 4 — an enterovirus, a virus transmitted through the intestines — may be able to trigger diabetes in people who have the virus.
A new study has shown a possible mechanism for triggering diabetes in people who have coxsackievirus B type 4 (CVB4), a type of enterovirus.
According to the Centers for Disease Control and Prevention (CDC), diabetes is an ongoing health condition that affects how a person’s body transforms food into energy.
As a person consumes food and drinks, their blood sugar increases. Their pancreas then produces the hormone insulin, which enables cells to access this blood sugar.
Type 2 diabetes is by far the most common form of diabetes, accounting for approximately 90–95% of all cases of diabetes in the adult population.
The American Diabetes Association consider both types of diabetes to be caused by a combination of genetic and environmental factors.
For type 1 diabetes, scientists believe that viruses are one aspect of these environmental factors.
In particular, research suggests that enteroviruses — a family of viruses that can cause a variety of diseases with “neurologic, respiratory, skin, and gastrointestinal” symptoms — may be key viral triggers for type 1 diabetes.
However, scientists are not yet sure exactly how this triggering function occurs.
In the present study, the researchers wanted to better understand how enteroviruses may trigger type 1 diabetes.
To do so, they used mice that had been grafted with human pancreatic cells with CVB4, as well as human and mouse insulin-producing cells that also had the virus.
After conducting various experiments with these infected cells, the researchers identified a complex chain of events that may account for the trigger of diabetes.
The researchers observed that CVB4 infection induced downregulation of URI, a protein that controls various cellular functions. This downregulation triggered a cascade of molecular events.
This in turn resulted in the silencing of the gene Pdx1, which governs the function of beta cells in the pancreas. These beta cells produce insulin.
As Dr. Nabil Djouder, a researcher at the Spanish National Cancer Research Center and the lead author of the study, explains, “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.”
Helping to corroborate their findings, the researchers also noted that mice with diabetes that overexpressed the URI protein were more tolerant of blood sugar changes.
Finally, the researchers noted a correlation between the expression of URI, Pdx1, and viral particles in pancreata from people with diabetes. For the scientists, this suggests a causal relation between human diabetes and enteroviruses.
As well as helping make clear the mechanism behind the viral triggering of diabetes, the study also raises the possibility of using antiviral therapies alongside drugs that inhibit the silencing of Pdx1 to prevent and treat diabetes.
The researchers demonstrated that DNA methyltransferase inhibitors, which inhibit a protein involved in the silencing of Pdx1, reinstated Pdx1 expression and glucose tolerance in diabetic mice.
The scientists believe that their study may also have implications for the COVID-19 pandemic. Dr. Djouder explains, “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.”
“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