Department of Pharmacy, The Second Affiliated Hospital of Shandong University of Chinese Medicine, Jinan, Shandong, China (mainland).
Teaching Experiment Training Center, Guangxi University of Chinese Medicine, Nanning, Guangxi, China (mainland).
Med Sci Monit. 2020 Sep 4;26:e924453. doi: 10.12659/MSM.924453.
BACKGROUND Type 2 diabetes (T2D) is characterized by ß-cell dysfunction and insulin resistance. Icariin (ICA), a flavonoid from Epimedium, possesses anti-diabetic and anti-inflammatory properties. However, it is unclear whether ICA acts on pancreatic ß-cells. The present study was designed to explore the effects and latent mechanism of ICA on uric acid (UA)-stimulated pancreatic b-cell dysfunction. MATERIAL AND METHODS Min6 cells were exposed to various concentrations of ICA for 24 h, and cell viability was assessed by MTT assays. Min6 cells were treated with ICA for 2 h, followed by 5 mg/dl UA for 24 h, and cell viability, apoptosis, apoptosis-associated protein levels and insulin secretion were assessed by MTT, flow cytometry, western blotting and glucose-stimulated insulin secretion assays, respectively. The effects of ICA and UA on the PI3K/Akt pathway were also analyzed by western blotting, as were the effects of the specific PI3K/Akt inhibitor LY294002. RESULTS ICA was not cytotoxic toward Min6 cells. UA decreased Min6 cell viability, enhanced cell apoptosis and levels of cleaved caspase-3, and reduced pro-caspase3 levels and insulin secretion, with all of these effects reversed by ICA in a dose-dependent manner. UA inhibited the PI3K/AKT pathway, an effect reversed by ICA treatment. The specific PI3K/Akt inhibitor LY294002, however, reversed these effects of ICA on UA-treated Min6 cells. CONCLUSIONS ICA protected Min6 cell function, an effect likely mediated by the PI3K pathway. ICA may inhibit the progression of diabetes.
2 型糖尿病（T2D）的特征是β细胞功能障碍和胰岛素抵抗。淫羊藿中的黄酮类化合物朝藿定（ICA）具有抗糖尿病和抗炎作用。然而，尚不清楚 ICA 是否作用于胰岛β细胞。本研究旨在探讨 ICA 对尿酸（UA）刺激的胰岛β细胞功能障碍的作用及其潜在机制。
将 Min6 细胞暴露于不同浓度的 ICA 24 h，通过 MTT 法评估细胞活力。用 ICA 处理 Min6 细胞 2 h，然后用 5 mg/dl UA 处理 24 h，通过 MTT、流式细胞术、Western blot 和葡萄糖刺激胰岛素分泌试验分别评估细胞活力、细胞凋亡、凋亡相关蛋白水平和胰岛素分泌。还通过 Western blot 分析 ICA 和 UA 对 PI3K/Akt 通路的影响，以及特异性 PI3K/Akt 抑制剂 LY294002 的影响。
ICA 对 Min6 细胞无细胞毒性。UA 降低 Min6 细胞活力，增强细胞凋亡和 cleaved caspase-3 水平，并降低 pro-caspase3 水平和胰岛素分泌，ICA 呈剂量依赖性逆转所有这些作用。UA 抑制 PI3K/AKT 通路，ICA 处理可逆转该作用。特异性 PI3K/Akt 抑制剂 LY294002 逆转了 ICA 对 UA 处理的 Min6 细胞的这些作用。
ICA 保护 Min6 细胞功能，该作用可能由 PI3K 通路介导。ICA 可能抑制糖尿病的进展。
