The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice

• Published in: Scientific reports Vol. 5; no. 1; p. 18325
• Main Authors: Kim, Ki-Suk, Jung Yang, Hea, Lee, In-Seung, Kim, Kang-Hoon, Park, Jiyoung, Jeong, Hyeon-Soo, Kim, Yoomi, Seok Ahn, Kwang, Na, Yun-Cheol, Jang, Hyeung-Jin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 17.12.2015
• Subjects: Aglycones; Animals; Cell Line, Tumor; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Enteroendocrine Cells - drug effects; Enteroendocrine Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Gene Expression - drug effects; Ginsenosides; Ginsenosides - pharmacology; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - metabolism; Glucose; Glucose tolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Hyperglycemia - complications; Hyperglycemia - prevention & control; Immunoblotting; Insulin; L cells; Mice, Inbred C57BL; Mice, Knockout; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA-mediated interference; Rodents; Secretion; Signal transduction; Sugar; Taste; Transducin - deficiency; Transducin - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18325

Ginsenosides can be classified on the basis of the skeleton of their aglycones. Here, we hypothesized that the sugar moieties attached to the dammarane backbone enable binding of the ginsenosides to the sweet taste receptor, eliciting glucagon-like peptide-1 (GLP-1) secretion in the enteroendocrine L cells. Using the human enteroendocrine NCI-H716 cells, we demonstrated that 15 ginsenosides stimulate GLP-1 secretion according to the position of their sugar moieties. Through a pharmacological approach and RNA interference technique to inhibit the cellular signal cascade and using the Gαgust(-/-) mice, we elucidated that GLP-1 secreting effect of Rg3 mediated by the sweet taste receptor mediated the signaling pathway. Rg3, a ginsenoside metabolite that transformed the structure through a steaming process, showed the strongest GLP-1 secreting effects in NCI-H716 cells and also showed an anti-hyperglycemic effect on a type 2 diabetic mouse model through increased plasma GLP-1 and plasma insulin levels during an oral glucose tolerance test. Our study reveals a novel mechanism where the sugar moieties of ginsenosides Rg3 stimulates GLP-1 secretion in enteroendocrine L cells through a sweet taste receptor-mediated signal transduction pathway and thus has an anti-hyperglycemic effect on the type 2 diabetic mouse model.