Ishikawa Tomohisa, Iwasaki Eri, Kanatani Kazumitsu, Sugino Fumi, Kaneko Yukiko, Obara Kazuo, Nakayama Koichi
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka-City, Shizuoka 422-8526, Japan.
Life Sci. 2005 Jun 10;77(4):462-9. doi: 10.1016/j.lfs.2005.01.008. Epub 2005 Feb 9.
The roles of protein kinase C (PKC) isoforms in cholinergic potentiation of glucose-induced insulin secretion were investigated in rat pancreatic islets. Western-blot analysis showed the presence of PKC-alpha, betaII, delta, epsilon, eta, and zeta, but not PKC-betaI, gamma, or iota, in the islets. Carbachol (CCh) caused translocations of PKC-alpha, betaII, delta, and epsilon from the cytosol to the plasma membrane. CCh facilitated 7-mM glucose-induced insulin secretion from isolated rat islets. The CCh-stimulated insulin secretion was significantly suppressed by the generic PKC inhibitor chelerythrine. In contrast, Go 6976, an inhibitor of conventional PKC isoforms, had no effect on the insulin secretion stimulated by CCh, although it significantly inhibited that induced by phorbol 12-myristate 13-acetate. These results suggest that the novel PKC isoforms activated by CCh, i.e., PKC-delta and/or epsilon, participate in the stimulatory effect of CCh on insulin secretion.
在大鼠胰岛中研究了蛋白激酶C（PKC）亚型在胆碱能增强葡萄糖诱导的胰岛素分泌中的作用。蛋白质印迹分析显示胰岛中存在PKC-α、βII、δ、ε、η和ζ，但不存在PKC-βI、γ或ι。卡巴胆碱（CCh）导致PKC-α、βII、δ和ε从细胞质转移到质膜。CCh促进了分离的大鼠胰岛中7 mM葡萄糖诱导的胰岛素分泌。CCh刺激的胰岛素分泌被通用PKC抑制剂白屈菜红碱显著抑制。相比之下，传统PKC亚型的抑制剂Go 6976对CCh刺激的胰岛素分泌没有影响，尽管它显著抑制了佛波酯12-肉豆蔻酸酯13-乙酸酯诱导的胰岛素分泌。这些结果表明，CCh激活的新型PKC亚型，即PKC-δ和/或ε，参与了CCh对胰岛素分泌的刺激作用。
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