Morgan N G, Montague W
Biochem J. 1982 Apr 15;204(1):111-25. doi: 10.1042/bj2040111.
delta-Haemolysin, a small surface-active polypeptide purified from the culture media of Staphylococcus aureus, was observed to stimulate the release of insulin from isolated rat islets of Langerhans. This effect was dose-dependent and saturable, with the half-maximal response elicited by a delta-haemolysin concentration of 10 micrograms/ml. Stimulation of insulin release by delta-haemolysin (10 micrograms/ml) was not dependent on the presence of glucose in the incubation medium, but was augmented by increasing concentrations of the sugar. The release of insulin in response to delta-haemolysin could be inhibited by depletion of extracellular Ca2+ or by adrenaline (epinephrine) (10 microM) and was readily reversible when delta-haemolysin was removed from the medium. In addition, the response was potentiated by incubation with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mM). These observations suggest that delta-haemolysin induced a true activation of the beta-cell secretory mechanism. Stimulation of islets of Langerhans with delta-haemolysin was found to be associated with a modest increase in intracellular cyclic AMP levels, although the adenylate cyclase activity of islet homogenates was not increased by delta-haemolysin. delta-Haemolysin was observed to induce a dose-dependent net accumulation of 45Ca2+ by islet cells and to stimulate the efflux of 45Ca2+ from preloaded islets. The efflux of 45Ca2+ was modest in size and short-lived, but dramatically increased in medium depleted fo 40Ca2+. Incubation in the presence of verapamil augmented delta-haemolysin-induced 45Ca2+ efflux and insulin secretion. delta-Haemolysin was found to be a potent 45Ca2+-translocating ionophore in an artificial system. This response was dose-dependent and could be augmented by verapamil. In addition, phosphatidylcholine (25 micrograms/ml) was found to inhibit both delta-haemolysin induced 45Ca2+ translocation and insulin release in a precisely parallel manner. These studies suggest that the ability of delta-haemolysin to stimulate insulin release may be due, in part, to the facilitation of Ca2+ entry into the beta-cells of islets of Langerhans, mediated directly by an ionophoretic mechanism.
δ-溶血素是一种从金黄色葡萄球菌培养基中纯化得到的小表面活性多肽，它能刺激分离的大鼠胰岛释放胰岛素。这种作用呈剂量依赖性且具有饱和性，δ-溶血素浓度为10微克/毫升时可引发半数最大反应。δ-溶血素（10微克/毫升）刺激胰岛素释放不依赖于孵育培养基中葡萄糖的存在，但随着糖浓度的增加而增强。细胞外Ca2+耗尽或肾上腺素（10微摩尔）可抑制δ-溶血素诱导的胰岛素释放，当从培养基中去除δ-溶血素时，这种释放很容易逆转。此外，与磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（0.2毫摩尔）孵育可增强反应。这些观察结果表明，δ-溶血素诱导了β细胞分泌机制的真正激活。尽管δ-溶血素未增加胰岛匀浆的腺苷酸环化酶活性，但发现用δ-溶血素刺激胰岛与细胞内环磷酸腺苷水平适度增加有关。观察到δ-溶血素可诱导胰岛细胞对45Ca2+的剂量依赖性净积累，并刺激预加载胰岛中45Ca2+的外流。45Ca2+的外流规模适中且持续时间短，但在缺乏40Ca2+的培养基中显著增加。在维拉帕米存在下孵育可增强δ-溶血素诱导的45Ca2+外流和胰岛素分泌。在人工系统中，δ-溶血素被发现是一种有效的45Ca2+转运离子载体。这种反应呈剂量依赖性，且可被维拉帕米增强。此外，发现磷脂酰胆碱（25微克/毫升）以精确平行的方式抑制δ-溶血素诱导的45Ca2+转运和胰岛素释放。这些研究表明，δ-溶血素刺激胰岛素释放的能力可能部分归因于通过离子载体机制直接促进Ca2+进入胰岛的β细胞。
