TAS2R46 activation protects intestinal barrier from chronic high glucose

Area of Science:

• Gastroenterology
• Molecular Biology
• Endocrinology

Background:

• The function of bitter taste receptor member 46 (TAS2R46) in the gut is largely unknown.
• Diabetes is known to cause intestinal barrier damage, but the underlying molecular mechanisms require further elucidation.

Purpose of the Study:

• To investigate the role of TAS2R46 signaling in ameliorating diabetic intestinal barrier injury.
• To clarify the molecular mechanisms by which TAS2R46 activation impacts gut health.

Main Methods:

• Utilized diabetic mouse models and high glucose-cultured Caco-2 cells.
• Administered TAS2R46 agonists (quinine, strychnine, hydrocortisone) and employed TAS2R46 blockage/knockdown.
• Performed PAS and H&E staining, Western blotting, and RNA sequencing.

Main Results:

• TAS2R46 agonists improved intestinal barrier function in diabetic mice and high glucose-treated cells, evidenced by increased tight junction proteins (Zonula occluden 1, occludin, E-cadherin) and improved morphology.
• Activation of TAS2R46 signaling was confirmed by increased expression of TAS2R46 and phospholipase C β2.
• TAS2R46 activation suppressed NF-κB signaling and was linked to the upregulation of SGK3 and SNX16.

Conclusions:

• TAS2R46 signaling activation alleviates intestinal barrier injury in diabetes.
• The protective effects are mediated through the SGK3/NF-κB pathway and the SNX16/E-cadherin axis.
• TAS2R46 represents a potential therapeutic target for diabetic gut complications.