Dihydromyricetin promotes GLP-1 release and glucose uptake by STC-1 cells and enhances the effects of metformin upon STC-1 cells and diabetic mouse model.

BACKGROUND:Glucagon-like peptide-1 (GLP-1) is an intestinally produced hormone released by the L-cells to stimulate glucose-dependent insulin release. Vine tea, a traditional Chinese medicine made from the delicate stem and leaves of Ampelopsis grossedentata, has been reported to exert antidiabetic effects; however, the role and mechanism of dihydromyricetin, the main active ingredient of vine tea, remain unclear. METHODS AND RESULTS:MTT assay was applied to detect cell viability. GLP-1 levels in the culture medium using a mouse GLP-1 ELISA kit. The level of GLP-1 in cells was examined using IF staining. NBDG assay was performed to evaluate the glucose uptake by STC-1 cells. The in vivo roles of dihydromyricetin in the diabetes mellitus mouse model were investigated. In this study, 25 μM dihydromyricetin, was found to cause no significant suppression of STC-1 cell viability. Dihydromyricetin markedly elevated GLP-1 secretion and glucose uptake by STC-1 cells. Although metformin increased GLP-1 release and glucose uptake by STC-1 cells more, dihydromyricetin further enhanced the effects of metformin. Moreover, dihydromyricetin or metformin alone significantly promoted the phosphorylation of AMPK, increased GLUT4 levels, inhibited ERK1/2 and IRS-1 phosphorylation, and decreased NF-κB levels, and dihydromyricetin also enhanced the effects of metformin on these factors. The in vivo results further confirmed the antidiabetic function of dihydromyricetin. CONCLUSION:Dihydromyricetin promotes GLP-1 release and glucose uptake by STC-1 cells and enhances the effects of metformin upon STC-1 cells and diabetic mice, which might ameliorate diabetes through improving L cell functions. The Erk1/2 and AMPK signaling pathways might be involved.