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Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation

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Recent advances in gut nutrient chemosensing.

C A Nguyen¹, Y Akiba, J D Kaunitz

¹Department of Nutrition, West Los Angeles VAMC, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA.

Current Medicinal Chemistry

|February 4, 2012

Summary

Gut nutrient chemosensing rapidly advances, identifying G protein-coupled receptors (GPCRs) and their ligands. This knowledge offers new therapeutic targets for metabolic disorders like diabetes and obesity.

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Area of Science:

Gastroenterology
Endocrinology
Molecular Biology

Background:

Gut nutrient chemosensing involves complex mechanisms where specific nutrients trigger metabolic responses.
G protein-coupled receptors (GPCRs) play a crucial role in sensing nutrients within the gut.
Deorphanization of gut GPCRs has revealed previously unknown receptors and their corresponding ligands.

Purpose of the Study:

To review nutrient receptors in the gut, their ligand specificities, and the resulting neurohormonal signaling pathways.
To highlight recent advances in understanding nutrient sensing mechanisms mediated by GPCRs.
To discuss the therapeutic potential of identified nutrient receptors and ligands.

Main Methods:

Review of scientific literature on gut nutrient chemosensing and GPCRs.
Analysis of identified GPCRs, including Family A (e.g., GPR93, FFA receptors) and Family C (e.g., mGluR, CaR, GPRC6A).
Discussion of ligand preferences for various nutrient receptors, including fatty acids, amino acids, carbohydrates, and tastants.

Main Results:

Family A GPCRs like GPR93 sense proteins, while FFA receptors (FFA1, FFA2, FFA3, GPR120) detect various chain-length fatty acids.
Family C receptors, including mGluR, CaR, and GPRC6A, are involved in L-amino acid sensing.
Taste receptors (sweet, bitter, umami) and potential carbohydrate sensors (T1R2/T1R3, SGLT-1) contribute to intestinal chemosensation.

Conclusions:

Specific nutrient receptors and their ligands have been identified, elucidating gut chemosensing pathways.
Understanding these nutrient-GPCR interactions provides a basis for novel therapeutic strategies.
Potential applications include treatments for metabolic diseases such as diabetes and obesity, as well as acid reflux and foregut mucosal injury.