Gao J, Liu M, Guo Z, Hu C, Feng Z, Yan J
Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Cooperation Research Center of Shanghai University of Traditional Chinese Medicine//Department of Endocrinology, Traditional Chinese Medicine Hospital of Jiading District, Shanghai 201899, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Jun 20;41(6):839-846. doi: 10.12122/j.issn.1673-4254.2021.06.05.
To explore the role of fetuin B-AMPK/ACC signaling pathway in mediating the effect of puerarin on hepatic insulin resistance in mice with type 2 diabetes mellitus (T2DM).
Forty C57BL/6J mouse models of T2DM induced by high-fat diet and intraperitoneal injection of streptozotocin were randomized into diabetic model (HFD) group and 3 puerarin groups for treatment with low-, moderate- and high- dose puerarin (50, 100 and 200 mg/kg, respectively), with another 10 mice fed a normal diet as the control group. After treatment for 8 weeks, the mice were examined for fasting blood glucose (FBG), fasting insulin (FINS), liver triglycerides (TG), cholesterol (TC) and free fatty acids (FFA) levels. The expression of fetuin B in the liver was detected by immunohistochemistry. RT-qPCR was used to detect the expressions of fetuin B, AMPK, and ACC mRNA in the liver, and the protein expressions of fetuin B, AMPKα1, ACC, P-AMPKαT183/T172, and P-ACC S79 were determined with Western blotting.
Treatment with moderate- and high-dose puerarin significantly lowered TG, TC, FFA and FBG levels in diabetic mice ( < 0.01). Puerarin at all the 3 doses significantly lowered FINS and HOMA-IR of the mice ( < 0.01). In diabetic mice, hepatic expressions of fetuin B and ACC mRNA increased and AMPK mRNA decreased significantly ( < 0.01); the protein expressions of fetuin B and ACC increased while those of AMPKα1, P-AMPKαT183/T172 and P-ACC S79 decreased significantly ( < 0.01). Puerarin dose-dependently inhibited the mRNA and protein expressions of fetuin B and ACC, increased AMPK mRNA and protein expressions of AMPKα1, P-AMPKαT183/ T172, and P-ACC S79, and lowered fetuin B content in the liver of diabetic mice ( < 0.01).
Puerarin alleviates insulin resistance and improves glucolipid metabolism in T2DM mice by modulating hepatic fetuin B-AMPK/ACC signaling pathway.
探讨胎球蛋白B-AMPK/ACC信号通路在介导葛根素对2型糖尿病（T2DM）小鼠肝脏胰岛素抵抗影响中的作用。
将40只通过高脂饮食联合腹腔注射链脲佐菌素诱导的C57BL/6J T2DM小鼠模型随机分为糖尿病模型（HFD）组和3个葛根素组，分别用低、中、高剂量葛根素（分别为50、100和200 mg/kg）进行治疗，另取10只喂食正常饮食的小鼠作为对照组。治疗8周后，检测小鼠的空腹血糖（FBG）、空腹胰岛素（FINS）、肝脏甘油三酯（TG）、胆固醇（TC）和游离脂肪酸（FFA）水平。采用免疫组织化学法检测肝脏中胎球蛋白B的表达。用RT-qPCR检测肝脏中胎球蛋白B、AMPK和ACC mRNA的表达，并用蛋白质印迹法测定胎球蛋白B、AMPKα1、ACC、P-AMPKαT183/T172和P-ACC S79的蛋白表达。
中、高剂量葛根素治疗可显著降低糖尿病小鼠的TG、TC、FFA和FBG水平（<0.01）。3种剂量的葛根素均显著降低了小鼠的FINS和HOMA-IR（<0.01）。在糖尿病小鼠中，肝脏中胎球蛋白B和ACC mRNA的表达增加，而AMPK mRNA显著降低（<0.01）；胎球蛋白B和ACC的蛋白表达增加，而AMPKα1、P-AMPKαT183/T172和P-ACC S79的蛋白表达显著降低（<0.01）。葛根素剂量依赖性地抑制糖尿病小鼠肝脏中胎球蛋白B和ACC的mRNA和蛋白表达，增加AMPKα1、P-AMPKαT183/T172和P-ACC S79的AMPK mRNA和蛋白表达，并降低肝脏中胎球蛋白B含量（<0.01）。
葛根素通过调节肝脏胎球蛋白B-AMPK/ACC信号通路减轻T2DM小鼠的胰岛素抵抗并改善糖脂代谢。
