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

Autor: Hossein Arefanian, Ashraf Al Madhoun, Fatema Al-Rashed, Fawaz Alzaid, Fatemah Bahman, Rasheeba Nizam, Mohammed Alhusayan, Sumi John, Sindhu Jacob, Michayla R. Williams, Nermeen Abukhalaf, Steve Shenouda, Shibu Joseph, Halemah AlSaeed, Shihab Kochumon, Anwar Mohammad, Lubaina Koti, Sardar Sindhu, Mohamed Abu-Farha, Jehad Abubaker, Thangavel Alphonse Thanaraj, Rasheed Ahmad, Fahd Al-Mulla
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cells, Vol 13, Iss 11, p 949 (2024)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells13110949
Popis: 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: Directory of Open Access Journals
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