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二氢杨梅素通过 STC-1 细胞促进 GLP-1 的释放和葡萄糖摄取,并增强二甲双胍对 STC-1 细胞和糖尿病小鼠模型的作用。

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.

机构信息

College of Biology and Food Engineering, Huaihua University. Key Laboratory of Research and Utilization of Ethnomedicinal Plant Resources of Hunan Province, Huaihua, China.

College of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.

出版信息

Tissue Cell. 2023 Jun;82:102108. doi: 10.1016/j.tice.2023.102108. Epub 2023 May 13.

DOI:10.1016/j.tice.2023.102108
PMID:37229936
Abstract

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.

摘要

背景

胰高血糖素样肽-1(GLP-1)是一种由 L 细胞分泌的激素,可刺激葡萄糖依赖性胰岛素释放。藤茶是一种传统的中药,由纤细的茎和葡萄科蛇葡萄属的叶子制成,已被报道具有降血糖作用;然而,藤茶的主要活性成分二氢杨梅素的作用和机制尚不清楚。

方法和结果

MTT 法检测细胞活力。用小鼠 GLP-1 ELISA 试剂盒检测培养基中的 GLP-1 水平。用 IF 染色法检测细胞内 GLP-1 水平。用 NBDG 法评估 STC-1 细胞的葡萄糖摄取。研究二氢杨梅素在糖尿病小鼠模型中的体内作用。在这项研究中,发现 25μM 二氢杨梅素对 STC-1 细胞活力没有明显的抑制作用。二氢杨梅素显著增加 STC-1 细胞的 GLP-1 分泌和葡萄糖摄取。虽然二甲双胍增加 STC-1 细胞的 GLP-1 释放和葡萄糖摄取更多,但二氢杨梅素进一步增强了二甲双胍的作用。此外,二氢杨梅素或二甲双胍单独使用均可显著促进 AMPK 磷酸化,增加 GLUT4 水平,抑制 ERK1/2 和 IRS-1 磷酸化,降低 NF-κB 水平,二氢杨梅素还增强了二甲双胍对这些因素的作用。体内结果进一步证实了二氢杨梅素的抗糖尿病作用。

结论

二氢杨梅素促进 STC-1 细胞 GLP-1 的释放和葡萄糖摄取,并增强二甲双胍对 STC-1 细胞和糖尿病小鼠的作用,可能通过改善 L 细胞功能来改善糖尿病。Erk1/2 和 AMPK 信号通路可能参与其中。

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