Unraveling Verapamil's Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models.

Autor: Arefanian H; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Al Madhoun A; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.; Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman 15462, Kuwait., Al-Rashed F; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Alzaid F; Department of Bioenergetics & Neurometabolism, Dasman Diabetes Institute, Dasman 15462, Kuwait.; Institut Necker Enfants Malades (INEM), French Institute of Health and Medical Research (INSERM), Immunity & Metabolism of Diabetes (IMMEDIAB), Université de Paris Cité, 75014 Paris, France., Bahman F; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Nizam R; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait., Alhusayan M; Department of Bioenergetics & Neurometabolism, Dasman Diabetes Institute, Dasman 15462, Kuwait., John S; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait., Jacob S; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait., Williams MR; Department of Bioenergetics & Neurometabolism, Dasman Diabetes Institute, Dasman 15462, Kuwait., Abukhalaf N; Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman 15462, Kuwait., Shenouda S; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Joseph S; Special Services Facilities, Dasman Diabetes Institute, Dasman 15462, Kuwait., AlSaeed H; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Kochumon S; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Mohammad A; Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Koti L; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait., Sindhu S; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait.; Animal and Imaging Core Facility, Dasman Diabetes Institute, Dasman 15462, Kuwait., Abu-Farha M; Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, Kuwait.; Department of Translational Research, Dasman Diabetes Institute, Dasman 15462, Kuwait., Abubaker J; Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Thanaraj TA; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait., Ahmad R; Department of Immunology & Microbiology, Dasman Diabetes Institute, Dasman 15462, Kuwait., Al-Mulla F; Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, Kuwait.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 May 30; Vol. 13 (11). Date of Electronic Publication: 2024 May 30.
DOI: 10.3390/cells13110949
Abstrakt: This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting β-cell functionality.
Databáze: MEDLINE
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