Arefanian, H.; Al Madhoun, A.; Al-Rashed, F.; Alzaid, F.; Bahman, F.; Nizam, R.; Alhusayan, M.; John, S.; Jacob, S.; Williams, M.R.; Abukhalaf, N.; Shenouda, S.; Joseph, S.; AlSaeed, H.; Kochumon, S.; Mohammad, A.; Koti, L.; Sindhu, S.; Abu-Farha, M.; Abubaker, J.; Thanaraj, T.A.; Ahmad, R.; Al-Mulla, F. Unraveling Verapamil’s Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models. Cells2024, 13, 949.
Arefanian, H.; Al Madhoun, A.; Al-Rashed, F.; Alzaid, F.; Bahman, F.; Nizam, R.; Alhusayan, M.; John, S.; Jacob, S.; Williams, M.R.; Abukhalaf, N.; Shenouda, S.; Joseph, S.; AlSaeed, H.; Kochumon, S.; Mohammad, A.; Koti, L.; Sindhu, S.; Abu-Farha, M.; Abubaker, J.; Thanaraj, T.A.; Ahmad, R.; Al-Mulla, F. Unraveling Verapamil’s Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models. Cells 2024, 13, 949.
Arefanian, H.; Al Madhoun, A.; Al-Rashed, F.; Alzaid, F.; Bahman, F.; Nizam, R.; Alhusayan, M.; John, S.; Jacob, S.; Williams, M.R.; Abukhalaf, N.; Shenouda, S.; Joseph, S.; AlSaeed, H.; Kochumon, S.; Mohammad, A.; Koti, L.; Sindhu, S.; Abu-Farha, M.; Abubaker, J.; Thanaraj, T.A.; Ahmad, R.; Al-Mulla, F. Unraveling Verapamil’s Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models. Cells2024, 13, 949.
Arefanian, H.; Al Madhoun, A.; Al-Rashed, F.; Alzaid, F.; Bahman, F.; Nizam, R.; Alhusayan, M.; John, S.; Jacob, S.; Williams, M.R.; Abukhalaf, N.; Shenouda, S.; Joseph, S.; AlSaeed, H.; Kochumon, S.; Mohammad, A.; Koti, L.; Sindhu, S.; Abu-Farha, M.; Abubaker, J.; Thanaraj, T.A.; Ahmad, R.; Al-Mulla, F. Unraveling Verapamil’s Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models. Cells 2024, 13, 949.
Abstract
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 resil-ience. 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 inflic-tion. 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 re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.
Medicine and Pharmacology, Endocrinology and Metabolism
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