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Antipsychotics inhibit the mitochondrial bioenergetics of pancreatic beta cells isolated from CD1 mice
Author(s) -
Elmorsy Ekramy,
Alelwani Walla,
Kattan Shahad,
Babteen Nouf,
Alnajeebi Afnan,
Ghulam Jihan,
Mosad Soad
Publication year - 2021
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13484
Subject(s) - mitochondrion , adenosine triphosphate , bioenergetics , haloperidol , inner mitochondrial membrane , membrane potential , biology , biochemistry , chemistry , microbiology and biotechnology , endocrinology , dopamine
Antipsychotics (APs) are widely used medications with reported diabetogenic side effects. This study investigated the effect of commonly used APs, namely chlorpromazine (CPZ), haloperidol (HAL) and clozapine, on the bioenergetics of male CD1 mice isolated pancreatic beta cells as an underlying mechanism of their diabetogenic effects. The effect of APs on Alamar blue reduction, adenosine triphosphate (ATP) production and glucose‐stimulated insulin secretion (GSIS) of isolated beta cells was evaluated. Then, the effects of APs on the activities of mitochondrial complexes and their common coding genes expression, oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and lactate production were investigated. The effects of APs on the mitochondrial membrane fluidity (MMF) and mitochondrial membrane fatty acid composition were also examined. Results showed that the tested APs significantly decreased cellular ATP production and GSIS of the beta cells. The APs significantly inhibited the activities of mitochondrial complexes and their coding gene expression, MMP and OCR of the treated cells, with a parallel increase in lactate production to different extents with the different APs. CPZ and HAL showed increased MMF and mitochondrial membrane polyunsaturated fatty acid content. In conclusion, the tested APs‐induced mitochondrial disruption can play a role in their diabetogenic side effect.