EFFECT OF OUABAIN ON INSULIN-SECRETION IN THE AMPHIBIAN PANCREAS

We investigated the influence of ouabain on glucose-induced insulin re lease from toad pancreatic minces in the same nanomolar range as that of an ouabain-like compound found in human blood. Ouabain increased in sulin secretion at basal (2 mM), but not maximally stimulatory (8 mM), glucose levels in a dose-dependent manner up to an optimal concentrat ion of 1 nM, with the values declining progressively thereafter. Ouaba in at 3 nM changed the shape of the overall dose-response curve for gl ucose from sigmoidal to hyperbolic and displaced the optimal insulinot ropic glucose concentration from 8 to 2 mM. Preincubation with ouabain (3 nM) followed by glycoside washout potentiated insulin induction at 2 mM, but not at 8 mM glucose, but this same pretreatment followed by incubation in Ca2+-free medium depressed insulin release under all co nditions, and especially at high glucose; here, however, the preexposu re to ouabain partially prevented the drop in insulin secretion at 8 m M glucose. Acetylcholine at 8 mu M augmented insulin release at both l evels of glucose, and ouabain potentiated this effect synergistically at high, but not low glucose. Ouabain, at physiologic concentrations, thus appears to regulate the effect of secretagogues such as glucose a nd acetylcholine in amphibians. (C) 1997 Elsevier Science Inc.