In type I diabetes, the immune system destroys insulin-producing “islet” cells in the pancreas, leaving patients dependent on insulin injections for life. In a strain of mice prone to develop the disease, researchers at the University of Toronto used an unusual approach to prevent this mistaken attack: they targeted sensory neurons.
Known by the abbreviation TRPV1, the neurons were originally identified as receptors for capsaicin (a highly painful chili pepper extract). In the pancreas, TRPV1 neurons weave through islet cells, binding tightly to insulin and playing a role in inflammation.
“We believe these neurons help the islet cell function optimally, but in patients with diabetes the circuit goes astray,” says lead author Hans-Michael Dosch of the university’s Hospital for Sick Children.
To test the theory, Dosch and his team used capsaicin to block TRPV1 neurons in diabetic mice. The team reported in the December 15 issue of Cell that in a third of the treated mice, islet cells were completely free of destructive immune activity; little inflammation was seen in the other two thirds.
Overall, the incidence of diabetes dropped about 80 percent, and the treatment delayed the onset of diabetes in the mice that did succumb. Equally striking, a small protein called substance P, secreted by sensory neurons, reversed the disease almost overnight when injected into the pancreas of animals that had begun to show symptoms.
“Our findings identify TRPV1 neurons as key players in type I diabetes and may open up new therapeutic avenues,” Dosch says.