Role of extracellular Na+ on CCK-8-induced insulin secretion

CCK-8 stimulates insulin secretion by an effect involving phosphoinositide (PI) hydrolysis and release of Ca2+ from intracellular stores. In this study, we examined the dependence of Na+ for the effects of CCK-8. CCK-8 (100 nM) stimulated insulin secretion from isolated rat islets. A first phase, which lasted 10 min, was not affected by removal of external Na+, whereas a second phase was abolished. CCK-8-stimulated 45Ca2+ and 3H efflux in 45Ca(2+)- and myo-[2-3H]-inositol-prelabelled islets were not affected by removal of external Na+. In a second series of experiments, pancreatic rat islet cells were loaded with the Ca2+ fluorophore FURA 2-AM. CCK-8 (100 nM) induced a rapid and transient increase in the cytoplasmic free Ca2+ concentration ([Ca2+]IC), followed by a subsequent reduction of [Ca2+]IC below the prestimulatory levels. The CCK-8-induced increase in [Ca2+]IC was not dependent on extracellular Na+, whereas the decline in [Ca2+]IC after the initial peak was slower in the absence than in the presence of Na+. Thus, the present study shows that both the second phase of CCK-8-stimulated insulin secretion and the CCK-8-stimulated postpeak reduction in [Ca2+]IC are dependent on extracellular Na+.