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High-Throughput Quantitative Screening of Glucose-Stimulated Insulin Secretion and Insulin Content Using Automated MALDI-TOF Mass Spectrometry.


ABSTRACT: Type 2 diabetes (T2D) is a metabolic disorder characterized by loss of pancreatic β-cell function, decreased insulin secretion and increased insulin resistance, that affects more than 537 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 β-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 β-cell function in a 384-well plate format, using the murine β-cell model Min6. By using MALDI-TOF mass spectrometry, we implemented a high-throughput screening (HTS) strategy based on the automation of a cellular assay allowing the detection of insulin secretion in response to glucose, i.e., the quantitative detection of insulin, in a miniaturized system. As a proof of concept, we screened siRNA targeting well-know β-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.

SUBMITTER: Delannoy CP 

PROVIDER: S-EPMC10047017 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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High-Throughput Quantitative Screening of Glucose-Stimulated Insulin Secretion and Insulin Content Using Automated MALDI-TOF Mass Spectrometry.

Delannoy Clément Philippe CP   Heuson Egon E   Herledan Adrien A   Oger Frederik F   Thiroux Bryan B   Chevalier Mickaël M   Gromada Xavier X   Rolland Laure L   Froguel Philippe P   Deprez Benoit B   Paul Sébastien S   Annicotte Jean-Sébastien JS  

Cells 20230309 6


Type 2 diabetes (T2D) is a metabolic disorder characterized by loss of pancreatic β-cell function, decreased insulin secretion and increased insulin resistance, that affects more than 537 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 β-cell function and insulin secretion remains crucial. Here, we developed an automat  ...[more]

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