Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced potentiation of leucine/glutamine-stimulated insulin secretion
Involvement of Ca2+/calmodulin kinase II (CaMK II) in genistein-induced potentiation of leucine/glutamine-stimulated insulin secretion
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DOI：
10.1007/s10059-009-0119-7
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发表时间：
2009-09-01
影响因子：
3.8
通讯作者：
Kang, Yup
中科院分区：
文献类型：
--
作者：
Lee, Soo-Jin;Kim, Hyo-Eun;Kang, Yup
据报道，金雀异黄素可增强葡萄糖刺激的胰岛素分泌(GSIS)。对酪氨酸激酶的抑制活性或蛋白激酶A(PKA)的激活在金雀异黄素诱导的GSIS增强效应中起作用。本研究旨在阐明金雀异黄素诱导胰岛素分泌增强的机制。金雀异黄素可增加INS-1细胞在葡萄糖、丙酮酸或亮氨酸/谷氨酰胺(Leu/Gln)等生能营养素刺激下的胰岛素分泌，但不能增加去极化试剂如KCl、甲苯丁胺或钙通道开放剂Bay K8644刺激的胰岛素分泌。50 mU M的染料木素对Leu/Gln刺激的胰岛素分泌有最大的促进作用，但不足以抑制酪氨酸激酶的活性。抑制剂研究和免疫印迹分析表明，PKA的激活在金雀异黄素诱导的亮氨酸/谷氨酰胺刺激的胰岛素分泌增强中几乎没有参与。另一方面，所有受试的钙/钙调蛋白激酶II抑制剂都显著减弱了染料木素诱导的增强作用。金雀异黄素还能增加细胞内[Ca~(2+)](I)和磷酸化CaMKⅡ的水平。此外，金雀异黄素还能增加CaMK II过表达的INS-1细胞由亮氨酸/谷氨酰胺刺激的胰岛素分泌。这些数据表明，CaMK II的激活在染料木素诱导的胰岛素分泌增强中起作用。
Genistein has been reported to potentiate glucose-stimulated insulin secretion (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A (PKA) was shown to play a role in the genistein-induced potentiation effect on GSIS. The aim of the present study was to elucidate the mechanism of genistein-induced potentiation of insulin secretion. Genistein augmented insulin secretion in INS-1 cells stimulated by various energy-generating nutrients such as glucose, pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by depolarizing agents such as KCl and tolbutamide, or Ca2+ channel opener Bay K8644. Genistein at a concentration of 50 mu M showed a maximum potentiation effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to inhibit the activity of tyrosine kinase. Inhibitor studies as well as immunoblotting analysis demonstrated that activation of PKA was little involved in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the other hand, all the inhibitors of Ca2+/calmodulin kinase II tested, significantly diminished genistein-induced potentiation. Genistein also elevated the levels of [Ca2+](i) and phospho-CaMK II. Furthermore, genistein augmented Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These data suggest that the activation of CaMK II played a role in genistein-induced potentiation of insulin secretion.