title: The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Ki-Suk
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Hea
authors.initials: H
authors.lastname: Jung Yang
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: In-Seung
authors.initials: IS
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Kang-Hoon
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.|Western Seoul Center, Korea Basic Science Institute, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 120-140, Republic of Korea.
authors.forename: Yoomi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Kwang
authors.initials: K
authors.lastname: Seok Ahn
authors.affiliation: Western Seoul Center, Korea Basic Science Institute, 150 Bugahyeon-ro, Seodaemun-gu, Seoul 120-140, Republic of Korea.
authors.forename: Yun-Cheol
authors.initials: YC
authors.lastname: Na
authors.affiliation: Department of Biochemistry, College of Korean Medicine, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701 Republic of Korea.
authors.forename: Hyeung-Jin
authors.initials: HJ
authors.lastname: Jang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D019858:Enteroendocrine Cells / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000517:prevention & control*; D015151:Immunoblotting; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015293:Transducin / Q000172:deficiency / Q000235:genetics
chemical_list: D036145:Ginsenosides; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; C075192:gustducin; C097367:ginsenoside Rg3; D052216:Glucagon-Like Peptide 1; D015293:Transducin