Studies on the interaction of staphylococcal delta haemolysin with isolated islets of Langerhans.

Delta haemolysin, a surface active polypeptide isolated from the culture media of Staphylococcus aureus, was found to stimulate the release of insulin from isolated rat islets of Langerhans. This effect was dose - dependent, saturable, readily reversible, and could not be, attributed to hormone leakage resulting from cell damage. Insulin release in response to delta haemolysin was sensitive to modulation by agents and conditions known to affect glucose induced insulin release, including epinephrine, 3- isobutyl -1-methyl xanthine and depletion of extracellular calcium. This suggested a true activation of the beta cell secretory mechanism by delta haemolysin. Delta haemolysin was found to elevate the intracellular cyclic AMP concentration in islet cells, an effect which was dependent on the presence of extracellular calcium and was probably not mediated by direct activation of adenylate cyclase. In addition, the toxin was observed to induce marked changes in islet cell calcium handling. It stimulated the uptake of 45Ca into islet cells and also caused a transient increase in the rate of 45ca efflux from pre-loaded islets. The characteristics of these responses were compatible with an ionophoretic mode of action. In an artificial 45Ca translocation system delta haemolysin was found to display potent ionophoretic properties. The sensitivity of the observed response to verapamil and phosphatidyl choline exactly paralleled the effects of these agents on delta haemolysin stimulated insulin release from isolated islets of Langerhans. It has been suggested that the ability of delta haemolysin to stimulate insulin release from isolated islets of Langerhans, may reflect, in part, a rise in the beta cell cytosolic calcium concentration, mediated directly, by the ionophoretic properties of the toxin molecule