The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization.
The digitonin-permeabilized pancreatic islet model. Effect of myo-inositol 1,4,5-trisphosphate on Ca2+ mobilization.
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洋地黄皂苷通透性胰岛模型。
DOI：
10.1042/bj2270965
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
McDaniel,ML
中科院分区：
文献类型：
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作者：
Wolf,BA;Comens,PG;Ackermann,KE;Sherman,WR;McDaniel,ML
葡萄糖诱导的胰岛素分泌被认为是介导的细胞内Ca 2+亚微摩尔增加，虽然细胞内的过程还没有得到很好的理解。我们已经使用先前表征的毛地黄皂苷透化的胰岛素分泌胰岛模型来研究肌醇1，4，5-三磷酸（IP 3）的作用，IP 3是一种公认的细胞内Ca 2+动员的第二信使。钙从内质网流出进行了研究，有或没有钒酸盐抑制钙再摄取。IP 3（10 μ M），在游离Ca 2+水平为0.06 μ M，增加Ca 2+释放30%，当钒酸盐存在时，增加50%。在10 μ M和2.5 μ M-IP 3下分别观察到最大和半最大Ca 2+释放。IP 3引起快速释放，然后缓慢再摄取。钒酸盐的存在下，再摄取减少。肌醇1，4-二磷酸、肌醇1-磷酸和其他磷酸肌醇代谢产物没有任何显著影响。由于Ca 2+水平在亚微摩尔范围内的增加先前已被证明能诱导毛地黄皂苷透化胰岛中的胰岛素释放，因此我们的结果与IP 3作为胰岛素分泌的第二信使的概念一致。
Glucose-induced insulin secretion is thought to be mediated by submicromolar increases in intracellular Ca2+, although the intracellular processes are not well understood. We have used the previously characterized digitonin-permeabilized insulin-secreting pancreatic islet model to study the role of myo-inositol 1,4,5-trisphosphate (IP3), a putative second messenger for mobilization of intracellular Ca2+. Ca2+ efflux from the endoplasmic reticulum was studied with or without vanadate present to inhibit Ca2+ reuptake. IP3 (10 microM), at a free Ca2+ level of 0.06 microM, increased Ca2+ release by 30% and, when vanadate was present, by 50%. Maximal and half-maximal Ca2+ release was observed at 10 microM- and 2.5 microM-IP3, respectively. IP3 provoked a rapid release that was followed by slow reuptake. Reuptake was diminished in the presence of vanadate. Inositol 1,4-bisphosphate, inositol 1-phosphate and other phosphoinositide metabolites did not have any significant effect. Because increases in Ca2+ levels in the submicromolar range have been previously shown to induce insulin release in digitonin-permeabilized islets, our results are consistent with the concept of IP3 serving as a second messenger for insulin secretion.