Hoa Nguyen Khanh, Norberg Ake, Sillard Rannar, Van Phan Dao, Thuan Nguyen Duy, Dzung Dang Thi Ngoc, Jörnvall Hans, Ostenson Claes-Göran
Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
J Endocrinol. 2007 Feb;192(2):389-94. doi: 10.1677/joe.1.06948.
We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3 x 3 and 16 x 7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 microM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3 x 3 mM glucose with 150 muM phanoside and 0 x 25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 microM phanoside alone. At 16 x 7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0 x 25 mM diazoxide (P<0 x 01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3 x 3 mM glucose but did not further increase the release at 16 x 7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3 x 3 mM glucose but decreased at 16 x 7 mM glucose (P<0 x 01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 microM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.
我们最近发现，从绞股蓝植物中分离出的绞股蓝皂苷（phanoside）可刺激大鼠胰岛分泌胰岛素。为研究绞股蓝皂苷刺激胰岛素分泌的机制，将正常Wistar（W）大鼠和自发性糖尿病Goto-Kakizaki（GK）大鼠的胰岛进行批量孵育或灌流。在3×3和16×7 mM葡萄糖浓度下，绞股蓝皂苷在W大鼠和糖尿病GK大鼠的胰岛中均能刺激胰岛素分泌增加数倍。在W大鼠胰岛的灌流实验中，绞股蓝皂苷（75和150 μM）剂量依赖性地增加胰岛素分泌，去除绞股蓝皂苷后胰岛素分泌恢复到基础水平。当W大鼠胰岛在3×3 mM葡萄糖浓度下与150 μM绞股蓝皂苷和0×25 mM二氮嗪一起孵育以保持K-ATP通道开放时，胰岛素分泌与仅在150 μM绞股蓝皂苷中孵育的胰岛相似。在16×7 mM葡萄糖浓度下，存在0×25 mM二氮嗪时，绞股蓝皂苷刺激的胰岛素分泌减少（P<0×01）。在被50 mM KCl去极化且存在二氮嗪的W大鼠胰岛中，绞股蓝皂苷在3×3 mM葡萄糖浓度下刺激胰岛素释放增加两倍，但在16×7 mM葡萄糖浓度下并未进一步增加释放量。当使用尼莫地平阻断β细胞中的L型Ca2+通道时，绞股蓝皂苷诱导的胰岛素分泌在3×3 mM葡萄糖浓度下不受影响，但在16×7 mM葡萄糖浓度下降低（P<0×01）。用百日咳毒素预处理胰岛以抑制胞吐作用的G蛋白，并不影响胰岛素对150 μM绞股蓝皂苷的反应。绞股蓝皂苷刺激W大鼠和GK大鼠胰岛分泌胰岛素。这种作用似乎在K-ATP通道和L型Ca2+通道的下游发挥，作用于β细胞的胞吐机制。
