Fagin J A, Ikejiri K, Levin S R
Research Service, Wadsworth VA Hospital, Los Angeles, CA 90073.
Diabetes. 1987 Dec;36(12):1448-52. doi: 10.2337/diab.36.12.1448.
Vanadium compounds are known to affect multiple membrane and cytosolic phosphoenzymes from various tissues; the most characterized effect is the inhibition of Na+-K+-ATPase. Since we previously reported that immunoreactive insulin (IRI) secretagogues tend to inhibit rat islet cation-dependent ATPases, we examined the effects of sodium vanadate on rat IRI secretion from incubated and perifused rat islets. In the presence of 2.4 mM Ca2+, vanadate (10(-3) M) induced biphasic IRI secretion with a background glucose of 100 mg/dl. In the absence of extracellular Ca2+, IRI released from incubated islets by vanadate at 100 and 300 mg/dl glucose was doubled and tripled, respectively. Furthermore, this stimulatory effect was completely abolished by known inhibitors of IRI release such as somatostatin, epinephrine, and diphenylhydantoin. Although we found the expected dose-dependent inhibition by vanadate of islet membrane Na+-K+-ATPase activity, the mechanism of action of vanadate on IRI secretion remains unknown. Vanadate probably interacts in a complex fashion with different islet phosphoenzymes and may prove to be a useful probe to further unravel the mechanisms leading to insulin secretion.
已知钒化合物会影响来自各种组织的多种膜和胞质磷酸酶；最显著的作用是抑制钠钾ATP酶。由于我们之前报道过免疫反应性胰岛素（IRI）促分泌剂往往会抑制大鼠胰岛阳离子依赖性ATP酶，因此我们研究了钒酸钠对孵育和灌注的大鼠胰岛分泌IRI的影响。在存在2.4 mM钙离子的情况下，钒酸盐（10⁻³ M）在背景葡萄糖浓度为100 mg/dl时诱导了双相IRI分泌。在无细胞外钙离子的情况下，钒酸盐在100和300 mg/dl葡萄糖浓度下从孵育的胰岛释放的IRI分别增加了一倍和两倍。此外，这种刺激作用被已知的IRI释放抑制剂如生长抑素、肾上腺素和苯妥英完全消除。尽管我们发现钒酸盐对胰岛膜钠钾ATP酶活性有预期的剂量依赖性抑制作用，但钒酸盐对IRI分泌的作用机制仍然未知。钒酸盐可能以复杂的方式与不同的胰岛磷酸酶相互作用，并且可能被证明是进一步揭示导致胰岛素分泌机制的有用探针。
