Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
PLoS One. 2014 Jan 3;9(1):e84550. doi: 10.1371/journal.pone.0084550. eCollection 2014.
Phosphatase and tensin homolog (PTEN) is a phosphoinositide phosphatase that regulates crucial cellular functions, including insulin signaling, lipid and glucose metabolism, as well as survival and apoptosis. Silymarin is the active ingredient in milk thistle and exerts numerous effects through the activation of PTEN. However, the effect of silymarin on the development of insulin resistance remains unknown.
Wistar rats fed fructose-rich chow or normal chow were administered oral silymarin to identify the development of insulin resistance using the homeostasis model assessment of insulin resistance and hyperinsulinemic- euglycemic clamping. Changes in PTEN expression in skeletal muscle and liver were compared using western blotting analysis. Further investigation was performed in L6 cells to check the expression of PTEN and insulin-related signals. PTEN deletion in L6 cells was achieved by small interfering ribonucleic acid transfection.
Oral administration of silymarin at a dose of 200 mg/kg once daily induced insulin resistance in normal rats and enhanced insulin resistance in fructose-rich chow-fed rats. An increase of PTEN expression was observed in the skeletal muscle and liver of rats with insulin resistance. A decrease in the phosphorylation of Akt in L6 myotube cells, which was maintained in a high-glucose condition, was also observed. Treatment with silymarin aggravated high-glucose-induced insulin resistance. Deletion of PTEN in L6 cells reversed silymarin-induced impaired insulin signaling and glucose uptake.
Silymarin has the ability to disrupt insulin signaling through increased PTEN expression. Therefore, silymarin should be used carefully in type-2 diabetic patients.
磷酸酶与张力蛋白同源物（PTEN）是一种磷酸肌醇磷酸酶，可调节胰岛素信号、脂质和葡萄糖代谢以及存活和细胞凋亡等重要细胞功能。水飞蓟素是奶蓟草的活性成分，通过激活 PTEN 发挥多种作用。然而，水飞蓟素对胰岛素抵抗发展的影响尚不清楚。
给予富含果糖的饲料或正常饲料喂养的 Wistar 大鼠口服水飞蓟素，使用稳态模型评估胰岛素抵抗和高胰岛素-正常血糖钳夹技术来鉴定胰岛素抵抗的发展。通过 Western 印迹分析比较骨骼肌和肝脏中 PTEN 表达的变化。在 L6 细胞中进一步进行检查，以检查 PTEN 和胰岛素相关信号的表达。通过小干扰核糖核酸转染实现 L6 细胞中 PTEN 的缺失。
每天口服 200mg/kg 的水飞蓟素会在正常大鼠中诱导胰岛素抵抗，并增强富含果糖饲料喂养大鼠的胰岛素抵抗。在胰岛素抵抗大鼠的骨骼肌和肝脏中观察到 PTEN 表达增加。在高葡萄糖条件下维持的 L6 肌管细胞中 Akt 的磷酸化也减少。水飞蓟素治疗加重了高葡萄糖诱导的胰岛素抵抗。在 L6 细胞中缺失 PTEN 可逆转水飞蓟素诱导的胰岛素信号和葡萄糖摄取受损。
水飞蓟素通过增加 PTEN 表达的能力破坏胰岛素信号。因此，在 2 型糖尿病患者中应谨慎使用水飞蓟素。
