title: Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides.
abstract: 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 KATP channel opener diazoxide (340 μM), and the Ca2+ channel blocker nifedipine (20 μM) 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.
authors: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors: Can
authors: C
authors: Liu
authors: Mian
authors: M
authors: Zhang
authors: Meng-Yue
authors: MY
authors: Hu
authors: Hai-Fang
authors: HF
authors: Guo
authors: Jia
authors: J
authors: Li
authors: Yun-Li
authors: YL
authors: Yu
authors: Shi
authors: S
authors: Jin
authors: Xin-Ting
authors: XT
authors: Wang
authors: Li
authors: L
authors: Liu
authors: Xiao-Dong
authors: XD
authors: Liu
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology; D013311:Streptozocin / Q000009:adverse effects*
chemical_list: D036145:Ginsenosides; D007004:Hypoglycemic Agents; D012503:Saponins; D013311:Streptozocin; D000244:Adenosine Diphosphate; D052216:Glucagon-Like Peptide 1; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium