Department of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR China.
Central Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, PR China.
J Pharmacol Sci. 2021 Jan;145(1):88-96. doi: 10.1016/j.jphs.2020.11.005. Epub 2020 Nov 20.
Ginsenoside Rb1 has been shown to have antidiabetic and anti-inflammatory effects. Its major metabolite, compound K (CK), can stimulate the secretion of glucagon-like peptide-1 (GLP1), a gastrointestinal hormone that plays a vital role in regulating glucose metabolism. However, the mechanism underlying the regulation of GLP1 secretion by compound K has not been fully explored. This study was designed to investigate whether CK ameliorates incretin impairment by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation in NCI-H716 cells. Using NCI-H716 cells as a model cell line for GLP1 secretion, we analyzed the effect of CK on the expression of RhoA/ROCK/YAP pathway components. Our results suggest that the effect of CK on GLP1 secretion depends on the anti-inflammatory effect of CK. We also demonstrated that CK can affect the RhoA/ROCK/YAP pathway, which is downstream of transforming growth factor β1 (TGFβ1), by maintaining the capacity of intestinal differentiation. In addition, this effect was mediated by regulating F/G-actin dynamics. These results provide not only the mechanistic insight for the effect of CK on intestinal L cells but also the molecular basis for the further development of CK as a potential therapeutic agent to treat type 2 diabetes mellitus (T2D).
人参皂苷 Rb1 已被证明具有降血糖和抗炎作用。其主要代谢物化合物 K（CK）可以刺激胰高血糖素样肽-1（GLP1）的分泌，GLP1 是一种在调节葡萄糖代谢中起关键作用的胃肠激素。然而，CK 调节 GLP1 分泌的机制尚未得到充分探索。本研究旨在探讨 CK 是否通过调节 RhoA/ROCKs/YAP 信号通路和 NCI-H716 细胞中的细胞骨架形成来改善肠促胰岛素功能障碍。使用 NCI-H716 细胞作为 GLP1 分泌的模型细胞系，我们分析了 CK 对 RhoA/ROCK/YAP 通路成分表达的影响。我们的结果表明，CK 对 GLP1 分泌的影响取决于 CK 的抗炎作用。我们还证明，CK 可以通过维持肠道分化能力来影响转化生长因子 β1（TGFβ1）下游的 RhoA/ROCK/YAP 通路。此外，这种作用是通过调节 F/G-肌动蛋白动力学来介导的。这些结果不仅为 CK 对肠道 L 细胞的作用提供了机制见解，也为进一步将 CK 开发为治疗 2 型糖尿病（T2D）的潜在治疗剂提供了分子基础。
