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

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-03, Vol.12 (6), p.849
• Main Authors: Delannoy, Clément Philippe, Heuson, Egon, Herledan, Adrien, Oger, Frederik, Thiroux, Bryan, Chevalier, Mickaël, Gromada, Xavier, Rolland, Laure, Froguel, Philippe, Deprez, Benoit, Paul, Sébastien, Annicotte, Jean-Sébastien
• Format: Article
• Language: English
• Subjects: Animals; Automation; Beta cells; Blood glucose; Catalysis; Cell culture; Chemical compounds; Chemical Sciences; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Glucose; Glucose - metabolism; Glucose - pharmacology; Health aspects; High-throughput screening; High-throughput screening (Biochemical assaying); High-Throughput Screening Assays; Humans; Humidity; Insulin; Insulin - metabolism; Insulin resistance; Insulin Secretion; Insulin, Regular, Human - metabolism; MALDI-TOF mass spectrometry; Mass spectrometry; Mass spectroscopy; Metabolic disorders; Methods; Mice; Pancreas; pancreatic beta cell; Peptides; Scientific imaging; Secretion; Secretions; siRNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; type 2 diabetes
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12060849

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.