Calcium-antagonists and islet function

Abstract

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 of¹³³Ba²⁺ by isolated islets was inhibited by Ca²⁺, Mg²⁺ and verapamil. Glucose increased¹³³Ba²⁺ net uptake, but only when sufficient Ba²⁺ had accumulated in the islets. Theophylline failed to affect¹³³Ba²⁺ 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-responsive effector system.