Bioluminescent Assay for the Quantification of Cellular Glycogen Levels.

Glycogen is a large polymer of glucose that functions as an important means of storing energy and maintaining glucose homeostasis. Glycogen synthesis and degradation pathways are highly regulated and their dysregulation can contribute to disease. Glycogen storage diseases are a set of disorders that arise from improper glycogen metabolism. Glycogen storage disease II, known as Pompe disease, is caused by a genetic mutation that leads to increased glycogen storage in cells and tissues, resulting in progressive muscle atrophy and respiratory decline for patients. One approach for treating Pompe disease is to reduce glycogen levels by interfering with the glycogen synthesis pathway through glycogen synthase inhibitors. To facilitate the study of glycogen synthase inhibitors in biological samples, such as cultured cells, a high-throughput approach for measuring cellular glycogen was developed. A bioluminescent glycogen detection assay was automated and used to measure the glycogen content in cells grown in 384-well plates. The assay successfully quantified reduced glycogen stores in cells treated with a series of glycogen synthase 1 inhibitors, validating the utility of the assay for drug screening efforts and demonstrating its value for therapy development and glycogen metabolism research.

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© 2024 The Authors. Published by American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare the following competing financial interest(s): This work was supported by Promega Corporation and Maze Therapeutics. D.L., G.V., J.V. are employees of Promega Corporation. R.C., H.M. are former employees and shareholders of Maze Therapeutics. J.C.U., D.T.B., K.M. are current employees and shareholders of Maze Therapeutics. The authors declare no other competing financial interests.