Pancreatic Beta Cells Interact With Vagal Sensory Neurons

By David Douglas

November 16, 2020

NEW YORK (Reuters Health) - Work in viral tracing, immunohistochemistry and mouse models suggests pancreatic islets are densely innervated by sensory neurons, many of vagal origin, according to Florida-based researchers.

Destroying visceral sensory nerves is known to impact pancreatic islet function, glucose metabolism and diabetes onset, "but how islet endocrine cells interact with sensory neurons has not been studied," Dr. Madina Makhmutova and colleagues at the University of Miami Miller School of Medicine, in Florida, note in Gastroenterology.

"Because visceral sensory innervation is a crucial component of homeostatic regulatory circuits," they add, "there is a need to understand how islets signal to sensory fibers."

As Dr, Makhmutova told Reuters Health by email, "The emerging field of bioelectronic medicine (electroceuticals) expects one day to treat diabetes by stimulating the vagus nerve to coerce the pancreatic beta cell to secrete insulin. The mechanisms through which the pancreas and other inner organs communicate with the vagus nerve, however, are poorly understood."

The team hypothesized that pancreatic islets "use serotonin as a signaling molecule to communicate with the brain via vagal afferents."

To characterize the sensory innervation of the pancreas, the researchers first investigated the pancreatic distribution of the sensory neuronal marker substance P across mouse strains using immunohistochemistry. This was consistent across strains.

The team initially established that under normal physiological conditions, serotonin is produced and released from mouse pancreatic islets in a glucose-dependent manner and that serotonin activates axonal terminals in the pancreatic islet. These responses were blocked by a serotonin-5HT2-receptor antagonist.

They then established that vagal sensory neurons respond to serotonin secreted from activated beta cells. Neurons in the vagal nodose ganglion responded in vivo to chemogenetic stimulation of beta cells and to pancreas infusion with serotonin, but were not sensitive to insulin.

Vagal activation by islet serotonin, the researchers suggest, "informs the brain about how much insulin is secreted in normal physiology as well as about the functional adaptations of the islet to physiological challenges."

However, they note that such a role for serotonin is controversial, and it "thus remains to be determined if the mechanism described in this study translates to human beings."

Nevertheless, Dr. Makhmutova concluded, "Our study shows that insulin-secreting beta cells activate vagus sensory neurons that project to the brain. Although the physiological role of this neuronal connection remains to be defined, our findings suggest that vagus-nerve manipulation (either stimulation or blockade) might have an effect on insulin secretion and glucose metabolism."

SOURCE: Gastroenterology, online October 26, 2020.