Study Uncovers A Specialized Gut-brain Pathway For Glucose Sensing

"How does nan encephalon separate glucose from nan galore nutrients absorbed successful nan gut?" In a groundbreaking study, a investigation squad astatine KAIST has uncovered a gut-brain circuit that enables nan encephalon to selectively admit glucose—beyond simply registering full caloric intake. This find opens a caller avenue for processing targeted strategies to power appetite and dainty metabolic disorders specified arsenic obesity and diabetes.

On July 9, KAIST (President Kwang Hyung Lee) announced that nan investigation was led by Professor Greg S.B. Suh of nan Department of Biological Sciences successful collaboration pinch Professor Young-Gyun Park (BarNeuro), Professor Seung-Hee Lee (Department of Biological Sciences), and researchers astatine Albert Einstein College of Medicine successful New York.

The squad demonstrated that, successful a authorities of hunger, animals are tin of detecting and preferentially selecting D-glucose successful nan gut via a specialized gut-brain circuit.

While it has agelong been known that nan gut transmits caloric accusation to nan encephalon to modulate appetite—primarily done suppressing hunger-related neurons successful nan hypothalamus—this study is nan first to uncover a nutrient-specific neural pathway that allows nan encephalon to observe glucose itself, not conscionable wide caloric content.

Using a operation of optogenetics, neural imaging, and nutrient infusions, nan researchers recovered that a subset of CRF neurons successful nan paraventricular nucleus (PVN) of nan hypothalamus respond selectively—and rapidly—to D-glucose introduced straight into nan mini intestine. These neurons did not respond, aliases responded inversely, to different nutrients for illustration L-glucose, amino acids, aliases fats.

Further mapping of nan pathway showed that D-glucose signals are conveyed from nan mini intestine to nan dorsolateral parabrachial nucleus (PBNdl) successful nan brainstem via nan spinal cord, and past relayed to CRF neurons successful nan PVN. This is successful opposition to signals from amino acids and fats, which recreation to nan encephalon via nan vagus nerve.

Inhibiting nan activity of CRF neurons successful fasting mice eliminated their earthy penchant for glucose, confirming nan necessity of this circuit for glucose-specific nutrient selection.

The study builds connected Professor Suh's earlier activity astatine NYU, wherever his squad identified DH44 neurons successful consequence flies that observe sweetener successful nan gut. Inspired by nan anticipation that mammals mightiness person akin glucose-sensing neurons, nan KAIST squad launched this investigation.

Dr. Jineun Kim (KAIST Ph.D., now astatine Caltech) played a starring domiciled successful nan study, demonstrating that fasting mice preferred glucose complete different nutrients delivered straight into nan tummy and that CRF neurons responded successful existent time. Wongyo Jung (KAIST B.S., now a Ph.D. student astatine Caltech) contributed modeling and behavioral analyses, while Dr. Shinhye Kim uncovered nan domiciled of circumstantial spinal neurons successful transmitting nutrient signals from nan gut to nan brain.

Drs. Kim and Kim noted,
"This study began pinch a elemental but basal question: How does nan encephalon separate glucose from different nutrients absorbed successful nan gut? We've shown that spinal-based gut-brain circuits play a cardinal domiciled successful maintaining power equilibrium and metabolic homeostasis."

Professor Suh added,
"By identifying a specialized gut-brain pathway for glucose sensing, this investigation opens up caller therapeutic possibilities for metabolic diseases. Moving forward, we purpose to analyse really akin circuits observe different basal nutrients, specified arsenic amino acids and fats, and really these systems interact."
Ph.D. student Jineun Kim, Dr. Shinhye Kim, and student Wongyo Jung (co-first authors) contributed to this study, which was published online successful nan world diary Neuron connected June 20, 2025.