Presentation Details
A New Tool to Identify and Pharmacologically Characterize GLP-1 Stimuli

Valentina Casà, Sara Montelatici, Laura Stucchi, Camilla Trovesi, Paola Bonetti, Stefania De Cesare, Alice Segnali, Loredana Redaelli, Viviana Agus, Alberto Di Silvio, Marcel Winnig.

Axxam SpA, Milan, Italy

Abstract


Enteroendocrine cells, comprising about 1% of the intestinal epithelium, are specialized cells that sense nutrients and mediate hormone secretion. Among them, enteroendocrine L-cells are responsible for secreting Glucagon-like Peptide-1 (GLP-1), which is essential for regulating appetite and glucose metabolism. GLP-1 promotes insulin secretion from the pancreas, suppresses appetite and contributes to weight loss. To detect GLP-1 secretion from enteroendocrine cell supernatants, we optimized and validated a GLP-1 secretion assay. We employed NCI-H716 and STC-1 cell lines, well-characterized models for human and murine intestinal L-cells, respectively, along with a reporter cell line that expresses the recombinant GLP-1 Receptor in combination with the chAMPion reporter system. Our high-throughput screening (HTS)-grade GLP-1 secretion assay was functionally assessed using carbohydrate stimuli, including fructose. Additionally, by testing specific receptor agonists, we confirmed a role for Bitter Taste Receptor 38 (TAS2R38) and Free Fatty Acid Receptor 4 (FFAR4, also known as GPR120) in stimulating GLP-1 release from NCI-H716 and STC-1 cells, respectively. In conclusion, we developed a powerful tool for identifying and pharmacologically profiling novel GLP-1 stimuli, demonstrating its applicability for the identification of new therapeutic strategies in the treatment of diabetes and obesity.

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