槲皮素和异槲皮苷通过LKB1-AMPKα途径抑制肝脏糖异生
Quercetin and Isoquercitrin Inhibiting Hepatic Gluconeogenesis Through LKB1-AMPKα Pathway.
作者信息
Chen L, Shen T, Zhang C P, Xu B L, Qiu Y Y, Xie X Y, Wang Q, Lei T
机构信息
Shanghai University of Traditional Chinese Medicine, Putuo Hospital, Dept. of Endocrinology, Shanghai, China.
出版信息
Acta Endocrinol (Buchar). 2020 Jan-Mar;16(1):9-14. doi: 10.4183/aeb.2020.9.
OBJECTIVE
To observe the impact of quercetin and isoquercitrin on gluconeogenesis in hepatocytes.
METHODS
Mouse primary hepatocytes were cultured with lactic acid and pyruvic acid. After treatment with quercetin and isoquercitrin for 24 hours, the glucose concentration in the culture supernatant was determined. RT-PCR was used to detect the mRNAs of PEPCK, G6Pase, LKB1, and AMPKα. Protein levels of LKB1, AMPKα, and Thr172 phosphorylation were evaluated by Western blot.
RESULTS
The glucose concentration in the gluconeogenesis group (GN) was significantly higher than in the control group (C), but the glucose concentrations in the high level quercetin(group 80Q) and high level isoquercitrin (group 80I) were significantly lower than in the group GN, P<0.01. In the group 80Q, and group 80I, the mRNA levels of PEPCK and LKB1were significantly lower than in the group GN (P<0.01), and the G6Pase mRNA were significantly lower than in the group GN (P<0.05). The protein levels of LKB1 and the phosphorylation of AMPKα Thr172 in the group 80Q, group 40I, and group 80I were higher than in the group GN. The effects of quercetin and isoquercitrin on LKB1 and AMPKα were similar to those of metformin.
CONCLUSIONS
Quercetin and isoquercitrin inhibit gluconeogenesis in hepatocytes, which may be related to the LKB1 upregulation and phosphorylation of AMPKα.
目的
观察槲皮素和异槲皮苷对肝细胞糖异生的影响。
方法
用乳酸和丙酮酸培养小鼠原代肝细胞。用槲皮素和异槲皮苷处理24小时后，测定培养上清液中的葡萄糖浓度。采用RT-PCR检测磷酸烯醇丙酮酸羧激酶（PEPCK）、葡萄糖-6-磷酸酶（G6Pase）、肝脏激酶B1（LKB1）和腺苷酸活化蛋白激酶α（AMPKα）的mRNA。通过蛋白质免疫印迹法评估LKB1、AMPKα的蛋白水平及Thr172位点的磷酸化水平。
结果
糖异生组（GN）的葡萄糖浓度显著高于对照组（C），但高剂量槲皮素组（80Q组）和高剂量异槲皮苷组（80I组）的葡萄糖浓度显著低于GN组，P<0.01。在80Q组和80I组中，PEPCK和LKB1的mRNA水平显著低于GN组（P<0.01），G6Pase的mRNA水平显著低于GN组（P<0.05）。80Q组、40I组和80I组中LKB1的蛋白水平以及AMPKα Thr172位点的磷酸化水平高于GN组。槲皮素和异槲皮苷对LKB1和AMPKα的作用与二甲双胍相似。
结论
槲皮素和异槲皮苷抑制肝细胞糖异生，这可能与LKB1上调及AMPKα磷酸化有关。
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