Mapping glucose-mediated gut-to-brain signalling pathways in humans

Area of Science:

• Neuroscience
• Gastroenterology
• Metabolic research

Background:

• Previous functional magnetic resonance imaging (fMRI) studies show glucose reduces hypothalamic blood-oxygen-level-dependent (BOLD) signals in humans.
• The central nervous system (CNS) mechanisms for glucose response remain unclear.
• Gastric emptying is slowed by glucose via the cholecystokinin (CCK1) receptor.

Purpose of the Study:

• To investigate the whole-brain response to glucose using physiological fMRI.
• To determine the role of CCK in the CNS response to glucose.
• To differentiate CCK1 receptor-dependent and -independent brain responses to glucose.

Main Methods:

• fMRI monitored BOLD signal changes in 12 healthy subjects.
• Intragastric infusion of 1M glucose with or without a CCK1 receptor antagonist (dexloxiglumide), or saline placebo.
• Measurements included gallbladder volume, blood glucose, insulin, GLP-1, CCK, and satiety scores.

Main Results:

• Intragastric glucose increased plasma glucose, insulin, and GLP-1, and decreased gallbladder volume (indicating CCK secretion).
• Glucose reduced BOLD signal in the brainstem, hypothalamus, cerebellum, occipital cortex, putamen, and thalamus.
• A CCK1 receptor antagonist blocked a glucose-induced BOLD signal increase specifically in the motor cortex.

Conclusions:

• Glucose elicits site-specific BOLD responses in the human brain.
• Brainstem and hypothalamic BOLD signal reduction is CCK1 receptor-independent, likely due to circulatory effects of glucose and insulin.
• The motor cortex exhibits an early, dexloxiglumide-reversible BOLD signal increase, indicating a CCK1 receptor-dependent neural pathway.