Long-term exposure to genistein improves insulin secretory function of pancreatic β-cells
Long-term exposure to genistein improves insulin secretory function of pancreatic β-cells
复制标题
DOI：
10.1016/j.ejphar.2009.06.005
复制
发表时间：
2009-08-15
影响因子：
5
通讯作者：
Liu, Dongmin
中科院分区：
文献类型：
--
作者：
Fu, Zhuo;Liu, Dongmin
我们最近发现金雀异黄素（一种植物来源的天然化合物）是胰腺 β 细胞中的一种新型 cAMP 信号激动剂。在本研究中，我们进一步表明，将克隆胰岛素分泌细胞（INS-1E）暴露于金雀异黄酮48小时可增强葡萄糖刺激的胰岛素分泌（GSIS），而胰岛素含量没有改变，这表明金雀异黄素增强的GSIS并不是由于胰岛素合成的调节。这种染料木黄酮效应与蛋白酪氨酸激酶和 K-ATP 通道无关。此外，金雀异黄素对葡萄糖转运蛋白2表达或细胞ATP产生没有影响，但同样增强了INS-1E细胞中丙酮酸刺激的胰岛素分泌，表明长期暴露金雀异黄素对胰岛素分泌功能的改善与葡萄糖摄取或糖酵解途径的改变无关。金雀异黄素增强的胰岛素分泌与细胞内 Ca2+ 浓度升高相关，并依赖于蛋白激酶 A 和新蛋白质合成，因为这种作用被 N-[2-对溴肉桂氨基)乙基]-5-异喹啉磺酰胺或放线菌酮完全阻断。同样，暴露 48 小时的金雀异黄素也增强了新鲜分离的小鼠和人类胰岛的 GSIS，这表明存在非物种特异性和生物学相关的效应。这些发现提供了证据表明金雀异黄素可能是一种新型生物活性化合物，它通过改善胰腺β细胞的胰岛素分泌而具有抗糖尿病作用。 (C) 2009 Elsevier B.V. 保留所有权利。
We recently found that genistein, a plant-derived natural compound, is a novel cAMP signaling agonist in pancreatic beta-cells. In the present study, we further show that exposure of clonal insulin secreting (INS-1E) cells to genistein for 48 h enhanced glucose-stimulated insulin secretion (GSIS), whereas insulin content was not altered, suggesting that genistein-enhanced GSIS is not due to a modulation of insulin synthesis. This genistein effect is protein tyrosine kinase- and K-ATP channel-independent. In addition, genistein had no effect on glucose transporter-2 expression or cellular ATP production, but similarly augmented pyruvate-stimulated insulin secretion in INS-1E cells, indicating that the improvement of insulin secretory function by long-term genistein exposure is not related to an alternation in glucose uptake or the glycolytic pathway. The enhanced insulin secretion by genistein was associated with elevated intracellular Ca2+ concentration and dependent on protein kinase A and new protein synthesis as this effect was completely blocked by N-[2-p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide or cycloheximide. Similarly, 48 h of genistein exposure also enhanced GSIS in freshly isolated mouse and human pancreatic islets, suggesting a non-species-specific and biologically relevant effect. These findings provide evidence that genistein may be a novel bioactive compound that has an anti-diabetic effect by improving insulin secretion from pancreatic beta-cells. (C) 2009 Elsevier B.V. All rights reserved.