Molecular Mechanisms used by GLP-1 Receptors to regulate secretion

Details

GLP-1 Receptor are G protein coupled receptors that naturally respond to glucagon-like peptide-1 (GLP-1), a hormone produced in the gut in response to food intake. The receptor is the target for the type 2 diabetes and weight loss drug semaglutide. Its actions in the pancreas are well studied however, little is known about the molecular mechanisms responsible for its regulation of secretion from neurons. Using a combination of high resolution live cell fluorescent imaging, electrochemistry and patch clamp electrophysiology, we recently discovered that activation of GLP-1Rs promotes the formation of stable fusion pores in adrenal chromaffin cells to facilitate peptide secretion. The aim of this project is to identify the signaling events and molecules controlling exocytosis which are regulated by GLP-1 receptors in neuro-endocrine cells. Investigations into ligand and location bias within this context could aid the development of the next generation of GLP-1 agonists for the treatment of diverse neurological and cardiovascular disorders.

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References

GONZÁLEZ-SANTANA, A., ESTÉVEZ-HERRERA, J., SEWARD, E. P., BORGES, R. & MACHADO, J. D. 2021. Glucagon-like peptide-1 receptor controls exocytosis in chromaffin cells by increasing full-fusion events. Cell Reports, 36, 109609. https://www.sciencedirect.com/science/article/pii/S2211124721010470?via%3Dihub

Seward Lab https://www.sheffield.ac.uk/biosciences/people/academic-staff/elizabeth-seward