PUBLICATION
Unraveling Verapamil's Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models
- Authors
- 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.
- ID
- ZDB-PUB-240620-9
- Date
- 2024
- Source
- Cells 13(11): (Journal)
- Registered Authors
- Jacob, Sindhu
- Keywords
- MIN6 cells, calcium channel blocker, diabetes mellitus, verapamil, zebrafish, β-cells
- MeSH Terms
-
- Cholecystokinin*/metabolism
- Cholecystokinin*/pharmacology
- Insulin/metabolism
- Cell Proliferation*/drug effects
- Glucose/metabolism
- Verapamil*/pharmacology
- Insulin-Secreting Cells*/drug effects
- Insulin-Secreting Cells*/metabolism
- Mice
- Zebrafish*
- Regeneration/drug effects
- Cell Line
- Animals
- Disease Models, Animal
- PubMed
- 38891081 Full text @ Cells
Citation
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. (2024) Unraveling Verapamil's Multidimensional Role in Diabetes Therapy: From β-Cell Regeneration to Cholecystokinin Induction in Zebrafish and MIN6 Cell-Line Models. Cells. 13(11):.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping