1763-P: Pretreatment with Verapamil Increases MIN6 Mouse ß-Cell Survival after Exposure to Cytotoxic Stressors

Verapamil was found to lower the risk of developing new-onset diabetes and to lower fasting glucose levels in persons with diabetes. While previous studies have focused on treatment with verapamil, our objective in this study was to determine the effect of verapamil pre-treatment on MIN6 mouse β cell-line viability in response to different stressors mimicking conditions of in vitro models of type 1 (T1D) and type 2 diabetes (T2D). MIN6 cells were treated with either streptozotocin (STZ), T1D-cytomix containing IL-1β, TNF-α, and INF-γ, or a T2D-cytomix containing IL-1β, TNF-α, and palmitic acid. MTT assay was performed to determine viability of the cells pre-treated with verapamil (50 µM) for 24 hours, followed by each stressor treatment for another 24 hours, under normal (5.6 mM) glucose conditions. For all stressors, pre-treatment with verapamil significantly increased the cell viability, compared to verapamil-untreated controls. To study the synergistic effect of verapamil pre-treatment on the combined treatment of verapamil plus stressors, MIN6 cells were pre-treated with verapamil, then exposed to co-treatment conditions. We found that co-treatment of verapamil with each stressor significantly improved the cell survival, compared to cells treated with the stressor only. In case of STZ and T2D-cytomix, pre-treatment of verapamil significantly increased the cell viability, compared to cells that only received co-treatment alone. No significant synergistic effect of verapamil was observed as pre-treatment on co-treatment of verapamil and T1D-cytomix. In all cases showing protective effect of verapamil pre-treatment, verapamil improved cell viability in a dose-dependent manner. These results suggest that verapamil may have cytoprotective effect in MIN6 β cells under conditions mimicking T1D/T2D insults, and pre-treatment with verapamil, in particular, offers higher protection.