Abstract
1. Acetylcholine potentiated glucose-stimulated insulin release from ob/ob-mouse islets in salt-balanced bicarbonate buffer and to a lesser extent in Tris buffer; basal insulin release at 3 mM-D-glucose was not affected. Potentiation required the presence of Ca(2+).2. In bicarbonate buffer, ACh stimulated the islet uptake of (45)Ca(2+) at 3 mM-glucose but not significantly at 11 mM; no effect was seen in Tris buffer.3. At 11 mM-glucose, ACh increased the fluorescence from Ca(2+)-chlorotetracycline in dispersed islet cells; the effect was inhibited by atropine.4. At both 3 and 11 mM-glucose, ACh stimulated the islet uptake of (22)Na(+) in 60 min. At 11 mM-glucose, (22)Na(+) uptake in 5 min was also enhanced significantly, and this effect was inhibited by atropine.5. At 3 mM-glucose, ACh probably stimulated the islet uptake of (86)Rb(+) in 10 min.6. ACh had no effect on (36)Cl(-) retention at 3 or 11 mM-glucose, or on the oxidation of D-[U-(14)C]glucose (11 mM).7. The insulin secretory potentiator, ACh, does not act by accelerating glucose oxidation and does not induce the same ionic effects as the secretory initiator, D-glucose. Increased Na(+) permeability and altered interaction of Ca(2+) with the plasma membrane may play roles in the cholinergic depolarization of beta-cells and potentiation of insulin release.