Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Diabetes Institute, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Biomed Pharmacother. 2021 May;137:111325. doi: 10.1016/j.biopha.2021.111325. Epub 2021 Feb 23.
Pueraria, a Chinese herbal medicine, plays an important role in many classic prescriptions for the treatment of diabetes. Puerarin is the main component of pueraria. The current in vivo and in vitro research mainly focus on exploring the potential mechanism of puerarin in inhibiting hepatic gluconeogenesis. The type 2 diabetic rats were established by a combination of small dosage of streptozotocin (STZ) injection with high-fat diet. After the administration of puerarin 4 weeks, the parameters of the glucose and lipid metabolism were determined. HepG2 cells were treated by palmitic acid (PA) to induce the insulin resistance in vitro model. After the treatment of puerarin, the glucose consumption and cell viability were examined. Then, the protein expression of PI3K, Akt, pAkt, pFOXO1, FOXO1, PEPCK and G6pase in liver tissue and HepG2 cells were evaluated by western blot. RT-PCR was used to measure the content of PEPCK, G6pase mRNA in liver tissue. The results showed that puerarin administration significantly decrease the level of FBG, HbA1C and triglycerides in diabetic rats. Mechanistic research showed that puerarin activating PI3K/Akt is puerarin-mediated beneficial effects and can be reversed by inhibitor of PI3K or Akt. In conclusion, puerarin inhibits hepatic gluconeogenesis by activating PI3K/Akt signaling pathway.
葛根，一种中药，在许多治疗糖尿病的经典方剂中发挥着重要作用。葛根素是葛根的主要成分。目前的体内和体外研究主要集中在探索葛根素抑制肝糖异生的潜在机制上。通过小剂量链脲佐菌素（STZ）注射与高脂肪饮食相结合的方法建立 2 型糖尿病大鼠模型。给予葛根素 4 周后，测定葡萄糖和脂质代谢参数。用棕榈酸（PA）处理 HepG2 细胞，在体外诱导胰岛素抵抗模型。给予葛根素处理后，检测葡萄糖消耗和细胞活力。然后，通过 Western blot 检测肝组织和 HepG2 细胞中 PI3K、Akt、pAkt、pFOXO1、FOXO1、PEPCK 和 G6pase 的蛋白表达。用 RT-PCR 测定肝组织中 PEPCK、G6pase mRNA 的含量。结果表明，葛根素给药可显著降低糖尿病大鼠的 FBG、HbA1C 和甘油三酯水平。机制研究表明，葛根素通过激活 PI3K/Akt 信号通路发挥有益作用，该作用可被 PI3K 或 Akt 的抑制剂逆转。综上所述，葛根素通过激活 PI3K/Akt 信号通路抑制肝糖异生。
