EndoC-βH5 human beta cells are ready-to-use functional human pancreatic beta cells. They robustly and reproducibly secrete insulin in response to both glucose and GLP-1/GIP receptor mediated potentiation. Insulin secretion measurement in EndoC-βH5 cells thus allow to measure dose responses to incretin analogs and to compare compound’s EC50s and maximum efficacies in a human beta cell environment, with endogenous receptor and signaling protein expression. In this study, we are now demonstrating that cAMP can also serve as a robust and rapid readout to measure GLP-1/GIP receptor signaling in these cells. We then compared EC50s and maximum efficacies obtained in glucose stimulated insulin secretion (GSIS) potentiation assay to those measured through cAMP production, this in order to characterize the predictivity of cAMP assays in the EndoC- βH5 human beta cell model. Overall, EndoC-βH5 cells, with several available readouts and endogenous expression of incretin receptor signaling machinery, is a powerful model to evaluate and compare the activity of incretin analogs on human beta cells and address the question of their mode of action in the case of pluri-receptor agonists.

Disclosure

M. Taurand: None. H. Olleik: Employee; Human Cell Design.

Funding

Pass Innovation Occitanie (France)

© 2024 by the American Diabetes Association
2024
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