Human blood glucose levels fluctuate continuously in response to diet and activities. While the overall changes in blood glucose have been extensively studied, the role of specific neurons in tracking these changes is not well understood.
Researchers at ETH Zürich recently explored the role of orexin neurons in monitoring blood glucose levels. Their findings, published in Nature Neuroscience, indicate that these neurons in the mouse brain track the rate at which blood glucose levels change.
“In the 2000s, there was significant research into ‘glucose-sensing neurons’ because these cells might affect brain function based on minute-to-minute bodily changes,” said Denis Burdakov, co-author of the study, to Medical Xpress. “With the ‘diabesity epidemic’ in countries like the U.K. and U.S., this research is crucial as sugar is a key factor.”
Burdakov’s lab, formerly at the University of Cambridge, helped identify glucose-sensing capabilities in orexin neurons between 2005 and 2011. These neurons, which produce the neurotransmitter orexin/hypocretin, are vital for regulating arousal, wakefulness, and appetite. Loss of orexin cells leads to narcolepsy, a condition marked by disrupted consciousness.
Previous studies primarily examined isolated orexin cells in petri dishes. Burdakov’s new study aimed to understand the role of these neurons in living animals and their relationship with blood glucose levels.
The research team measured the real-time activity of live orexin neurons alongside glucose fluctuations in the blood. They used electrochemical glucose sensors in arteries and gene-targeted fluorescent activity reporters in the brain to monitor orexin cell responses.
Their findings revealed that orexin neurons are most active during the rise and fall of blood glucose waves, tracking the rate-of-change rather than absolute glucose levels. This suggests that orexin cells are crucial for sensing dynamic glucose changes, an important aspect of physiological regulation.
“Engineering principles highlight the importance of rate-of-change sensing for timely control,” Burdakov noted. “Our study shows that brain glucose sensors emit control signals based on glucose rate-of-change, rather than absolute levels.”
These insights have significant implications for understanding brain function and could influence dietary strategies to modulate brain activity. The study also found that mice without orexin neurons struggled to adjust their running behavior to glucose levels.
The ETH Zürich team’s findings pave the way for further research on orexin neurons and their influence on cognitive and emotional brain circuits.
