Genetic Variants Increasing TAS2R38 Bitter Taste Receptor Sensitivity Are Associated With Lower Postprandial Glycemia

The TAS2R38 bitter taste receptor, recently identified within intestinal L cells, has been shown to modulate GLP-1 secretion in preclinical models; however, evidence in humans remains limited. We harnessed functional variants comprising three canonical diplotypes of TAS2R38 to study the role of TAS2R38 in glucose homeostasis in humans. In a large sample of adults without type 2 diabetes, we found that individuals with more sensitive TAS2R38 receptors had lower postprandial glucose levels, independent of diet and lifestyle habits. Our findings provide evidence in humans supporting direct TAS2R38 actions in postprandial glycemia and highlight TAS2R38 as a potential therapeutic target for impaired glucose regulation.