College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi, China.
College of Life Sciences, Northwest University, 229 North Taibai Road, Xi'an, Shaanxi, China.
Arch Med Res. 2018 Jul;49(5):314-322. doi: 10.1016/j.arcmed.2018.10.005. Epub 2018 Nov 5.
Hepatic gluconeogenesis plays an important role in regulating fasting plasma glucose levels and is a target of anti-diabetic drugs. Several kinds of iridoid glucosides exhibit hypoglycemic effect, whereas the mechanism was not clear.
In this study, the effects of geniposide and gentiopicroside, two natural iridoid glucosides, on hepatic gluconeogenesis were investigated.
Glucose uptake assay, MTT assay, q-PCR, luciferase assay and western blot assay were performed to investigate the pharmacological effect of geniposide and gentiopicroside on human liver cell line L02. Thereby the fast blood glucose and intraperitoneal glucose tolerance were measured in high fat diet induced hyperglycemic mice after geniposide or gentiopicroside administration.
The results showed that geniposide and gentiopicroside inhibited the transcription of G6PC and PEPCK in L02 cells and in mice. Additional experimental data indicated that these two compounds were able to inhibit the transcriptional activity of FOXO1 by inducing phosphorylation of AKT at Ser473. Furthermore, we found that these two compounds alleviated high fat diet induced hyperglycemia in mice.
Geniposide and gentiopicroside might reduce blood glucose and suppress hepatic gluconeogenesis by regulating the AKT-FOXO1 pathway, and the potential use of these two iridoid glucosides as anti-diabetic agents merits further in-depth exploration.
肝糖异生在调节空腹血糖水平方面起着重要作用，是抗糖尿病药物的作用靶点。几种裂环环烯醚萜苷类化合物具有降血糖作用，但作用机制尚不清楚。
本研究旨在探讨天然裂环环烯醚萜苷京尼平苷和龙胆苦苷对肝糖异生的影响。
采用葡萄糖摄取实验、MTT 实验、q-PCR、荧光素酶实验和 Western blot 实验，研究京尼平苷和龙胆苦苷对人肝 L02 细胞系的药理作用。然后，在高脂饮食诱导的高血糖小鼠中，给予京尼平苷或龙胆苦苷后，检测快速血糖和腹腔内葡萄糖耐量。
结果表明，京尼平苷和龙胆苦苷抑制了 L02 细胞和小鼠中 G6PC 和 PEPCK 的转录。进一步的实验数据表明，这两种化合物通过诱导 AKT 在 Ser473 位点磷酸化，抑制 FOXO1 的转录活性。此外，我们发现这两种化合物可缓解高脂饮食诱导的小鼠高血糖。
京尼平苷和龙胆苦苷可能通过调节 AKT-FOXO1 通路降低血糖并抑制肝糖异生，这两种裂环环烯醚萜苷类化合物作为抗糖尿病药物的潜在用途值得进一步深入探讨。
