Kalwat, Michael A.2023-05-082023-05-082021Kalwat MA. High-Throughput Screening for Insulin Secretion Modulators [published correction appears in Methods Mol Biol. 2021;2233:C1]. Methods Mol Biol. 2021;2233:131-138. doi:10.1007/978-1-0716-1044-2_9https://hdl.handle.net/1805/32846The application of forward chemical genetics to insulin secretion in high-throughput has been uncommon because of high costs and technical challenges. However, with the advancement of secreted luciferase tools, it has become feasible for small laboratories to screen large numbers of compounds for effects on insulin secretion. The purpose of this chapter is to outline the methods involved in high-throughput screening for small molecules that chronically impact pancreatic beta cell function. Attention is given to specific points in the protocol that help to improve the dynamic range and reduce variability in the assay. Using this approach in 384-well format, at least 48 and as many as 144 plates can theoretically be processed per week. This protocol serves as a guideline and can be modified as required for alternate stimulation paradigms and improved upon as new technologies become available.en-USPublisher PolicyGaussia luciferaseHigh-throughput screeningInsulin secretionPancreatic beta cellsSmall moleculesArticle