Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides
Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides
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胰高血糖素样肽-1 分泌增加可能与人参皂苷的抗糖尿病作用有关
DOI：
10.1530/joe-12-0502
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发表时间：
2013-05-01
影响因子：
4
通讯作者：
Liu, Xiao-dong
中科院分区：
文献类型：
--
作者：
Liu, Can;Zhang, Mian;Liu, Xiao-dong
人参是最受欢迎的草药之一。人参皂苷是人参的主要生物活性成分，具有良好的抗糖尿病作用，但其作用机制尚不完全清楚。胰高血糖素样肽-1 （Glucagon-like peptide-1, GLP1）被认为是一种重要的肠促胰岛素，可以在餐后调节胃肠道内的葡萄糖稳态。本研究旨在探讨人参总皂苷（GTS）是否通过调节GLP1的释放来发挥其抗糖尿病作用。选择GTS中含量最高的成分人参皂苷Rb1 (Rb1)，进一步探讨其在NCI-H716细胞培养中的作用机制。采用高脂饮食和低剂量链脲佐菌素联合治疗糖尿病大鼠。糖尿病大鼠每日口服GTS(150或300 mg/kg) 4周。结果发现，GTS治疗可显著改善高血糖和血脂异常，并伴有葡萄糖诱导的GLP1分泌显著增加和胰高血糖素原基因表达上调。NCI-H716细胞的数据显示，GTS和Rb1均促进GLP1的分泌。Rb1增加了细胞内ATP / ADP浓度的比值和细胞内Ca2+浓度。代谢抑制剂叠氮化物（3mm）、K-ATP通道开启剂二氮氧化物（340 μ M）和Ca2+通道阻滞剂硝苯地平（20 μ M）显著逆转rb1介导的GLP1分泌。这些结果表明，人参皂苷在体内和体外均能刺激GLP1的分泌。人参皂苷的抗糖尿病作用可能是增强GLP1分泌的结果。
Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca2+ concentration. The metabolic inhibitor azide (3 mM), the K-ATP channel opener diazoxide (340 mu M), and the Ca2+ channel blocker nifedipine (20 mu M) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion.