Calcium-antagonists and islet function. VI. Effects of barium.

The modality of Ba2+-induced insulin release was investigated in the isolated perfused rat pancreas. The insulinotropic action of Ba2+ was antagonized by Ca2+, Mg2+ and verapamil, and enhanced by EGTA, theophylline, glucose and cytochalasin B. Likewise the net uptake of 133Ba2+ by isolated islets was inhibited by Ca2+, Mg2+ and verapamil. Glucose increased 133Ba2+ net uptake, but only when sufficient Ba2+ had accumulated in the islets. Theophylline failed to affect 133Ba2+ net uptake. These data suggest that (i) Ba2+-induced insulin release is dependent on the accumulation of this cation in the B-cell; (ii) Ba2+ inward transport in the B-cell occurs through a verapamil-sensitive channel characterized by competition between Ba2+, Ca2+ and Mg2+; and (iii) the enhancing effect of theophylline upon insulin release could be due to an intracellular translocation of alkaline-earth cations rather than to an increase in their net uptake. The present findings also support the idea that insulin release can be triggered by the accumulation of suitable divalent cations in a critical site of the B-cell, leading to the activation of a cytochalasin B-response effector system.