Persaud S J, Jones P M, Howell S L
Biomedical Sciences Division, King's College London, UK.
Mol Cell Endocrinol. 1993 Jul;94(1):55-60. doi: 10.1016/0303-7207(93)90051-k.
Staurosporine has been used in several studies to investigate the role of protein kinase C (PKC) in secretory responses of islets of Langerhans to insulin secretagogues. We have assessed the effect of staurosporine on: [i] islet PKC activity in vitro; [ii] the stimulation of insulin secretion by nutrient secretagogues and [iii] the stimulation of protein phosphorylation and insulin secretion in electrically permeabilised islets. All experiments were carried out on rat isolated islets of Langerhans, either intact or permeabilised by high voltage discharge (3.4 kV/cm). The activity of PKC partially purified from rat islets was inhibited by staurosporine (1.6-400 nM) in a concentration-dependent manner. Staurosporine also inhibited insulin secretion stimulated by both glucose and glyceraldehyde, with maximal effects at 50 nM. After prolonged exposure of islets to the tumour-promoting phorbol ester, 4 beta phorbol myristate acetate (4 beta PMA), a procedure which depletes islet PKC activity, staurosporine still inhibited both glucose- and glyceraldehyde-stimulated insulin release. In electrically permeabilised islets, staurosporine inhibited both Ca(2+)- and cyclic AMP-stimulated protein phosphorylation and insulin secretion. These results suggest that staurosporine should not be used as a selective inhibitor of PKC in rat islets.
在多项研究中已使用星形孢菌素探讨蛋白激酶C（PKC）在胰岛对胰岛素促分泌剂的分泌反应中的作用。我们评估了星形孢菌素对以下方面的影响：[i]体外胰岛PKC活性；[ii]营养性促分泌剂对胰岛素分泌的刺激作用；以及[iii]电透化胰岛中蛋白磷酸化和胰岛素分泌的刺激作用。所有实验均在大鼠分离的胰岛上进行，胰岛要么完整，要么通过高压放电（3.4 kV/cm）透化。从大鼠胰岛中部分纯化的PKC活性被星形孢菌素（1.6 - 400 nM）以浓度依赖的方式抑制。星形孢菌素还抑制葡萄糖和甘油醛刺激的胰岛素分泌，在50 nM时作用最大。在胰岛长时间暴露于促肿瘤佛波酯4β-佛波醇肉豆蔻酸酯（4β-PMA）（该过程会消耗胰岛PKC活性）后，星形孢菌素仍抑制葡萄糖和甘油醛刺激的胰岛素释放。在电透化胰岛中，星形孢菌素抑制钙（Ca²⁺）和环磷酸腺苷（cAMP）刺激的蛋白磷酸化及胰岛素分泌。这些结果表明，在大鼠胰岛中，星形孢菌素不应被用作PKC的选择性抑制剂。
