Biphasic Electrical Stimulation Promotes Insulin Release

Abstract

Biphasic (anodal pulse followed immediately by a cathodal pulse) electrical stimulation (10Hz, 5 ms duration) of rat insulinoma (Ins‐1) cells resulted in a 2–3‐fold increase in insulin release over 30 min that was stimulation period‐ and voltage‐dependent. Electrical stimulation of tissue culture medium (in the absence of cells) did not increase insulin release when subsequently added to cells, confirming that the insulin released by electrical stimulation was not due to substances generated by the culture medium. Electrical stimulation‐induced insulin release occurred in the absence or presence of glucose. Calcium channel blockade (using nifedipine or verapamil) inhibited basal insulin secretion and insulin secretion evoked by electrical stimulation, demonstrating that electrical stimulation‐induced insulin release involved activation of voltage‐dependent calcium channels and was not a non‐specific effect of stimulation on the plasma membrane. Basal insulin secretion and the increase in insulin release induced by electrical stimulation were also inhibited by the mitochondrial poisons antimycin A or oligomycin A, suggesting a role for mitochondrial function in insulin secretion. Electrical stimulation of cells also resulted in a more pronounced uptake of MitoTracker Red by mitochondria, indicating a more negative inner mitochondrial membrane potential. The failure of cells to accumulate the fluorogenic dye Cytotox green confirmed that electrical stimulation was not significantly disrupting the plasma membrane or inducing overt toxicity to the cells during the period of stimulation. These results provide further evidence that biphasic electrical stimulation can exert significant biological effects and elicit insulin release in a manner that is dependent upon mitochondrial activity and calcium channel activation but independent of glucose.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.