Gilon, PatrickBelhaj Aissa, FatmaFatmaBelhaj Aissa2025-02-042025-02-042023https://dial-mem.test.bib.ucl.ac.be/handle/123456789/36046The Islets of Langerhans play a critical role in the maintenance of glucose homeostasis. Within these islets, distinct α, β, and δ-cells hold key responsibilities. β-cells secrete insulin to modulate glucose uptake, while α-cells release glucagon to stimulate glucose release. Notably, δ-cells produce somatostatin (SST), a pivotal regulator of these processes. SST acts as an inhibitor, restraining the secretion of both insulin and glucagon. Furthermore, hormones produced within the islet regulate the functioning of nearby cells through paracrine modulation. In recent decades, research has shown limited focus on the δ-cell and the regulation of SST secretion by glucose given the scarcity of this type of cell within the islet. This thesis seeks to address this gap by investigating the mechanisms that govern δ-cell responses to glucose, specifically focusing on changes in cytosolic calcium concentration ([Ca2+]c), SST secretion, and cAMP levels. Additionally, given the presence of glucagon and GLP1 receptors on δ-cells, as well as glucagon's impact on insulin secretion, we explore the hypothesis that glucagon might stimulate SST secretion via GLP-1 receptors (GLP1R) under low glucose conditions. Simultaneously, we delve into the potential involvement of β-cells in δ-cell regulation, specifically examining the possibility of electrical coupling between these two cell types. Our investigation into δ-cell control by glucose has unveiled that increased glucose concentrations trigger SST secretion through mechanisms involving ATP-sensitive potassium channels, along with amplifying pathways. Furthermore, our findings concerning the role of glucagon in SST secretion under glucose conditions indicate that glucagon predominantly enhances SST secretion via GLP1R mechanisms, facilitated by an elevation in cAMP levels. Lastly, our study of β-δ cell coupling suggests a dynamic interaction between these cell types facilitated by gap junctions, enabling the synchronization of their Ca2+ oscillations.SSTglucagoninsulintext::thesis::master thesisthesis:38455