PUBLICATION
Verapamil Restores β-Cell Mass and Function in Diabetogenic Stress Models via Proliferation and Mitochondrial Respiration
- Authors
- Arefanian, H., Al-Rashed, F., Alzaid, F., Bahman, F., Abukhalaf, N., Alsaeed, H., Kochumon, S., Williams, M.R., Kidwai, S.M., Alhamar, G., Ahmad, R., Al-Mulla, F., Al Madhoun, A.
- ID
- ZDB-PUB-251113-22
- Date
- 2025
- Source
- Cells 14: (Journal)
- Registered Authors
- Keywords
- T1D, T2D, diabetes, verapamil
- MeSH Terms
-
- Humans
- Cell Proliferation/drug effects
- Insulin-Secreting Cells*/drug effects
- Insulin-Secreting Cells*/metabolism
- Insulin-Secreting Cells*/pathology
- Cell Line
- Mitochondria*/drug effects
- Mitochondria*/metabolism
- Verapamil*/pharmacology
- Cell Respiration/drug effects
- Mice
- Animals
- Zebrafish
- PubMed
- 41227341 Full text @ Cells
Citation
Arefanian, H., Al-Rashed, F., Alzaid, F., Bahman, F., Abukhalaf, N., Alsaeed, H., Kochumon, S., Williams, M.R., Kidwai, S.M., Alhamar, G., Ahmad, R., Al-Mulla, F., Al Madhoun, A. (2025) Verapamil Restores β-Cell Mass and Function in Diabetogenic Stress Models via Proliferation and Mitochondrial Respiration. Cells. 14:.
Abstract
Diabetes remains a global health challenge, characterized by persistent hyperglycemia and gradual depletion or impairment of pancreatic β-cells. Current treatments focus on managing glycemic control, but do not mitigate β-cell mass. Verapamil, an FDA-approved calcium channel blocker for hypertension, has shown potential therapeutic action towards β-cells in the context of diabetes. In this study, we investigated the cytoprotective and metabolic efficacy of verapamil on mouse-derived MIN6 β-cells under metabolic and diabetogenic stressors like high glucose, toxins, and an inflammatory cytokine cocktail, as well as investigated a zebrafish model. At safe, non-toxic doses, verapamil elevated the levels of cholecystokinin (CCK), an incretin associated with β-cell preservation and enhanced mitochondrial respiration. Notably, pretreatment and co-treatment of verapamil in the presence of stressors offered substantial protection and preserved mitochondrial function, whereas post-treatment effects were moderate and model dependent. In the zebrafish model, verapamil promoted β-cell recovery and regeneration before, during, and after targeted ablation. The drug seemed to work in several ways: inducing proliferation, reducing stress on β cells, boosting their energy production, and activating survival signals. Together, our data aligned with earlier human clinical trials showing that verapamil administration preserved β-cell mass and function in patients with recent-onset type 1 diabetes. The high efficacy, affordability, and broad mechanisms of action make verapamil a desirable therapeutic candidate for diabetes. Nevertheless, further mechanistic studies and long-term clinical trials are warranted to establish its utility in diabetes management.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping