In a study published in the journal Gastroenterology, researchers at the University of Miami Miller School of Medicine have shown that pancreatic beta cells release serotonin to communicate with the vagus nerve (which takes in signals from gastrointestinal organs) and ultimately the brain. This is the first time that scientists have shown how beta cells communicate with the brain via sensory nerves and that serotonin — not insulin — is the signaling molecule.
“The pancreas communicates with the brain using serotonin, which in the pancreas is mostly produced by beta cells,” said Alejandro Caicedo, Ph.D., professor of medicine and senior author on the study. “We have demonstrated how the pancreas and beta cells send data to the brain; we just don’t know yet what the brain is doing with that information.”
To better understand these signaling mechanisms, Madina Makhmutova, Ph.D., a postdoctoral researcher in Dr. Caicedo’s lab and first author on the paper, developed an approach for recording activity from vagal sensory neurons to investigate how signals from the pancreas reach the brain. One of the team’s main challenges was specificity — they wanted to stimulate only beta cells, which comprise just 4% of the pancreas, and not the whole organ.
“We were inspired by other sensory fields that study taste, hearing and smell,” said Dr. Makhmutova. “Researchers look at the peripheral signal transduction in the organ, and then they try to decode that information at the primary sensory neuron and understand how it is processed in the brain.”
Because the pancreas is not a sensory organ, the researchers had to find creative ways to stimulate it. Dr. Makhmutova developed a number of approaches, including gaining direct access to the pancreas and exposing it to serotonin, insulin and other compounds.
Tracking serotonin signaling
They also embraced a pharmacogenetic approach, in which they programmed beta cells to express a designer receptor that responds to clozapine N-oxide (CNO). With these, they were able to track serotonin signaling from beta cells through the vagus nerve. They found this signaling pathway produces a surprising amount of activity, indicating that the brain unconsciously receives large data packets every second from internal organs.
The study also showed beta cells release insulin and serotonin simultaneously, which may help the brain track when insulin has been released.
“By sensing serotonin, we believe these nerves are actually sensing how much the beta cells are working,” Dr. Caicedo said. “This may act like a thermostat, with the brain making minute adjustments as needed.”
Much more work needs to be done to determine how the brain reacts to this information and whether it has any impact on glucose metabolism. However, simply outlining the nerve pathways that connect pancreas and brain could provide new research avenues and, potentially, therapies.
“There is a huge initiative among companies, government agencies and doctors to stimulate nerves therapeutically,” Dr. Caicedo said. “So, this study fits well within that framework of electroceuticals or electronic medicine. Now that we understand the anatomy, researchers can start manipulating the vagus nerve and perhaps influence beta cells in some positive way.”