地锦草水提取物通过调节高脂饮食和链脲佐菌素诱导的2型糖尿病小鼠的糖异生和糖原合成改善肝脏葡萄糖稳态。

Water Extract of Bunge Improves Hepatic Glucose Homeostasis by Regulating Gluconeogenesis and Glycogen Synthesis in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice.

作者信息

Li Tiange, Chang Rui, Zhang Huijuan, Du Min, Mao Xueying

机构信息

Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.

Department of Animal Sciences, Washington State University, Pullman, WA, United States.

出版信息

Front Nutr. 2020 Sep 15;7:161. doi: 10.3389/fnut.2020.00161. eCollection 2020.

Abstract

Bunge, as a traditional Chinese medicine, exhibits many phytochemical activities. The aim of the present study was to investigate the effects of Bunge water extract (PDBW) and its underlying mechanisms on gluconeogenesis and glycogen synthesis in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mice. LC-MS/MS analyses of PDBW identified 6 major compounds including apigenin-7-O-β-D-glucoside, epicatechin, quercetin 3-O-β-D-glucuronide, kaempferol-3-O-β-D-glucopyranoside, scutellarin, and quercitrin. In the study, a mouse model of type 2 diabetes was induced by 4-week HFD combined with STZ (40 mg/kg body weight) for 5 days. After oral administration of PDBW at 400 mg/kg body weight daily for 8 weeks, the mice with type 2 diabetes showed significant decrease in the levels of fasting blood glucose and glycated hemoglobin A1c (HbA1c), and increase in the insulin level. PDBW improved the glucose tolerance, insulin sensitivity and lipid profiles. Furthermore, PDBW inhibited the mRNA levels of key gluconeogenic enzymes [phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase)] in liver. PDBW also promoted glycogen synthesis by raising the liver glycogen content, decreasing the phosphorylation of glycogen synthase (GS) and increasing the phosphorylation of glycogen synthase kinase3β (GSK3β). Besides, PDBW induced the activation of protein kinase B (Akt) and AMP-activated protein kinase (AMPK), which might explain changes in the phosphorylation of above enzymes. In summary, PDBW supplementation ameliorates metabolic disorders in a HFD/STZ diabetic mouse model, suggesting the potential application of PDBW in prevention and amelioration of type 2 diabetes.

摘要

地锦草作为一种传统中药,具有多种植物化学活性。本研究旨在探讨地锦草水提取物(PDBW)对高脂饮食/链脲佐菌素(HFD/STZ)诱导的2型糖尿病小鼠糖异生和糖原合成的影响及其潜在机制。对PDBW进行液相色谱-串联质谱(LC-MS/MS)分析,鉴定出6种主要化合物,包括芹菜素-7-O-β-D-葡萄糖苷、表儿茶素、槲皮素3-O-β-D-葡萄糖醛酸苷、山柰酚-3-O-β-D-吡喃葡萄糖苷、灯盏花素和槲皮苷。在本研究中,通过4周高脂饮食联合链脲佐菌素(40 mg/kg体重)处理5天诱导建立2型糖尿病小鼠模型。以400 mg/kg体重的剂量每日口服PDBW,持续8周后,2型糖尿病小鼠的空腹血糖和糖化血红蛋白A1c(HbA1c)水平显著降低,胰岛素水平升高。PDBW改善了葡萄糖耐量、胰岛素敏感性和血脂谱。此外,PDBW抑制了肝脏中关键糖异生酶[磷酸烯醇式丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酶(G6Pase)]的mRNA水平。PDBW还通过提高肝脏糖原含量、降低糖原合酶(GS)的磷酸化水平和增加糖原合酶激酶3β(GSK3β)的磷酸化水平来促进糖原合成。此外,PDBW诱导蛋白激酶B(Akt)和AMP活化蛋白激酶(AMPK)的激活,这可能解释了上述酶磷酸化的变化。综上所述,补充PDBW可改善HFD/STZ糖尿病小鼠模型的代谢紊乱,提示PDBW在预防和改善2型糖尿病方面具有潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66da/7522508/1dcac0efa811/fnut-07-00161-g0001.jpg

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