Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion.
Influence of staurosporine on glucose-mediated and glucose-conditioned insulin secretion.
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星形孢菌素对葡萄糖介导和葡萄糖调节的胰岛素分泌的影响。
DOI：
10.1042/bj2790807
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Rasmussen,H
中科院分区：
文献类型：
--
作者：
Zawalich,WS;Zawalich,KC;Ganesan,S;Calle,R;Rasmussen,H
研究了星形孢菌素（一种推定的蛋白激酶 C (PKC) 抑制剂）对葡萄糖和 4-甲基-2-氧代戊酸 (KIC) 诱导的胰岛素分泌的影响。此外，还检查了星形孢菌素对其他激动剂（葡萄糖作为条件调节剂）作用的影响。在 20 nM 浓度下，无论是由 10 mM 或 20 mM 葡萄糖、15 mM-KIC 还是由与 7.0 mM 葡萄糖共同灌注的胰岛中的卡巴胆碱或甲苯磺丁脲刺激，星形孢菌素均会显着抑制第二相胰岛素分泌。在每种情况下，第二相分泌反应均被抑制 70-85%。相反，在所有情况下，星形孢菌素对胰岛素分泌的第一阶段的强度和第一阶段分泌的时间过程没有影响，除非单独使用葡萄糖作为促分泌剂。无论是 10 mM 或 20 mM 葡萄糖，胰岛素分泌第一阶段的峰值都会延迟。星形孢菌素不会改变葡萄糖代谢，或葡萄糖激活磷酸肌醇水解或导致 α-PKC 易位至膜的能力。这些发现支持这样的概念：PKC 激活在燃料诱导或燃料调节的胰岛素分泌中发挥重要作用。
The effect of staurosporine, a putative inhibitor of protein kinase C (PKC), on insulin secretion induced by glucose and 4-methyl-2-oxopentanoate (KIC) was examined. In addition, the effects of staurosporine on the actions of other agonists, for which glucose acts as a conditional modifier, were also examined. At 20 nM, staurosporine caused a marked inhibition of second-phase insulin secretion, whether it was stimulated by 10 mM- or 20 mM-glucose, by 15 mM-KIC, or by carbachol or tolbutamide in islets co-perifused with 7.0 mM-glucose. In each case, the second-phase secretory response was inhibited by 70-85%. In contrast, in all cases there was no effect of staurosporine on the magnitude of the first phase of insulin secretion, nor on the time course of first-phase secretion, except when glucose alone was the secretagogue. With either 10 mM- or 20 mM-glucose, the peak of the first phase of insulin secretion was delayed. Staurosporine does not alter glucose metabolism, or the ability of glucose to activate phosphoinositide hydrolysis or to cause the translocation of alpha-PKC to the membrane. These findings support the concept that PKC activation plays an important role in fuel-induced or fuel-conditioned insulin secretion.