High glucose exposure impairs L-Cell differentiation in intestinal organoids: molecular mechanisms and clinical implications

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Agnese Filippello

University of Catania, Italy

: Endocrinol Diabetes Res

Abstract

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The differentiation of enteroendocrine cells (EECs) is a process regulated in the gut by a complex regulatory network. The effect of glucotoxicity, in the modulation of regulatory networks controlling identity and differentiation of EECs, has not been analyzed. This research aimed to study the effect of chronic hyperglycemia on EEC differentiation in mouse small intestinal organoids. Intestinal organoids were cultured in the presence or absence of high glucose concentrations for 48 h to mimic the diabetic state. Glucotoxicity impaired the expression of markers related to the differentiation of EEC progenitors (Ngn3) and L-cells (NeuroD1), and it reduced the expression of Gcg and GLP-1 positive cell numbers. In addition, the expression of intestinal stem cell markers was reduced in organoids treated with high glucose concentrations. Our results indicate that glucotoxicity impairs L-cell differentiation. This finding provides the identification of targets involved in new molecular signaling mechanisms impaired by glucotoxicity in the intestine.

Biography

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Agnese Filippello phD., has a major scientific interest in translational medicine and organoid research. She is an expert in organoid isolation from human and mouse tissues, molecular and cellular biology of organoids, and others cell lines. The main goals and responsibilities are represented by the molecular characterization organoids and 3D organoid live imaging involved in different types of diseases.