High-throughput quantitative screening of glucose-stimulated insulin secretion and insulin content using automated MAL-DI-TOF mass spectrometry

Delannoy, C. P.; Heuson, E.; Herledan, A.; Oger, F.; Thiroux, B.; Chevalier, M.; Gromada, X.; Rolland, L.; Froguel, P.; Deprez, B.; Paul, S.; Annicotte, J.-S.

doi:10.1101/2023.02.14.528514

bioRxiv · 10.1101/2023.02.14.528514

High-throughput quantitative screening of glucose-stimulated insulin secretion and insulin content using automated MAL-DI-TOF mass spectrometry

Delannoy, C. P.·Heuson, E.·Herledan, A.·Oger, F.·Thiroux, B.·Chevalier, M.·Gromada, X.·Rolland, L.·Froguel, P.·Deprez, B.·Paul, S.·Annicotte, J.-S.

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Abstract

Type 2 diabetes (T2D) is a metabolic disorder characterized by loss of pancreatic {beta}- cell function, decreased insulin secretion and increased insulin resistance, that affects more than 400 million people worldwide. Although several treatments are proposed to patients suffering from T2D, long-term control of glycemia remains a challenge. Therefore, identifying new potential drugs and targets that positively affect {beta}-cell function and insulin secretion remains crucial. Here, we developed an automated approach to allow the identification of new compounds or genes potentially involved in {beta}-cell function in a 384-well plate format, using the murine {beta}-cell model Min6. Using MALDI-TOF mass spectrometry, we have implemented a high-throughput screening (HTS) strategy based on the automation of a cellular assay allowing to detect insulin secretion in response to glucose, quantitative detection of insulin, in a miniaturized system. As a proof of concept, we screened siRNA targeting well-know {beta}-cell genes and 1600 chemical compounds and identified several molecules as potential regulators of insulin secretion and/or synthesis, demonstrating that our approach allows HTS of insulin secretion in vitro.

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Delannoy, C. P., Heuson, E., Herledan, A., Oger, F., Thiroux, B., Chevalier, M., Gromada, X., Rolland, L., Froguel, P., Deprez, B., Paul, S., Annicotte, J.-S.. 2023-02-15. High-throughput quantitative screening of glucose-stimulated insulin secretion and insulin content using automated MAL-DI-TOF mass spectrometry. https://doi.org/10.1101/2023.02.14.528514

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