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Updated: Jun 13, 2026
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Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation
Published on: December 29, 2023
Hypothalamic POMC neurons regulate intestinal glucose absorption via a gut-brain circuit
Hyo Sun Lim1, Se Hee Min2, Hyo Jin Kim3
1Department of Biomedical Science, University of Ulsan College of Medicine, Seoul, South Korea.
Nature Communications
|June 11, 2026
Summary
Activating protein kinase A (PKA) in hypothalamic POMC neurons improves glucose tolerance by reducing intestinal glucose absorption via the PKA-vagal-gut SGLT1 axis, offering a potential antidiabetic target.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Gastrointestinal Physiology
Background:
- Hypothalamic proopiomelanocortin (POMC) neurons regulate energy balance and glucose homeostasis.
- Protein kinase A (PKA) signaling is activated in POMC neurons by nutrients and antidiabetic agents.
- The precise role of PKA in POMC neurons' metabolic control is not fully understood.
Purpose of the Study:
- To investigate the metabolic regulatory role of PKA signaling in hypothalamic POMC neurons.
- To determine the effects of constitutive PKA activation in POMC neurons on glucose homeostasis and related pathways.
- To elucidate the mechanism by which PKA signaling influences intestinal glucose absorption.
Main Methods:
- Generated mice with POMC-specific constitutive PKA activation by depleting Prkar1a.
- Assessed metabolic parameters including body weight, glucose tolerance, insulin resistance, and hormone levels.
- Investigated neural pathways and intestinal mechanisms, including vagal nerve activity and sodium/glucose cotransporter-1 (SGLT1) function.
Main Results:
- POMC-specific PKA activation led to obesity and hypercortisolism but improved glucose tolerance.
- Improved glucose tolerance was linked to reduced intestinal glucose absorption and increased fecal glucose excretion.
- PKA activation in POMC neurons stimulated vagal motor neurons, suppressing SGLT1-dependent intestinal glucose absorption.
Conclusions:
- The POMC PKA signaling pathway plays a crucial role in regulating glucose homeostasis.
- The identified POMC PKA signaling-vagal-gut SGLT1 axis represents a novel mechanism for controlling intestinal glucose absorption.
- This axis is a potential therapeutic target for managing insulin resistance and type 2 diabetes.
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