ginsenoside-rg3 and Hyperglycemia

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.

Topics: Animals; Cell Line, Tumor; Diabetes Mellitus, Type 2; Enteroendocrine Cells; Enzyme-Linked Immunosorbent Assay; Gene Expression; Ginsenosides; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperglycemia; Immunoblotting; Mice, Inbred C57BL; Mice, Knockout; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Transducin

Ginsenosides, the active component of Panax ginseng, have been shown to evidence a variety of biological activities associated with hyperglycemia, obesity and type 2 diabetes mellitus. This study evaluated the effects of the ginsenosides, Rg3 and Re, on glucose uptake and the glucose transport system in mature 3T3-L1 cells. The results demonstrated that the glucose uptake of ginsenosides Rg3 and Re at concentrations of 1-10 µM significantly increased by approximately ∼10% and ∼12%, respectively. Furthermore, the glucose transporter 4 (GLUT4) mRNA expression of ginsenosides Rg3 and Re at 10 µM was increased by approximately ∼1.73 and 1.43 fold, respectively. It was further confirmed in a series of experiments that ginsenosides Rg3 and Re stimulated the mRNA expression of insulin receptor substrate (IRS-1) and the expression of phosphatidylinositol 3-kinase (PI3K)-110α protein, which is involved in downstream events in the insulin signaling pathway. These findings demonstrate that ginsenosides Rg3 and Re may stimulate glucose uptake via the PI3K pathways involving IRS-1. Further, our results suggest that both of these ginsenosides might prove useful as effective antidiabetic and antihyperglycemic agents.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Biological Transport; Diabetes Mellitus, Type 2; Ginsenosides; Glucose; Glucose Transporter Type 4; Hyperglycemia; Insulin Receptor Substrate Proteins; Mice; Panax; Phosphatidylinositol 3-Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction