Mechanism of <italic style="font-style: italic">Momordica charantia</italic> Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats

XU Guangyuan; ZHANG Zhuo; ZHANG Xiaoming

doi:10.13422/j.cnki.syfjx.20231122

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Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats

更新时间：2023-07-18

- Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 16, Pages: 65-71(2023)
- 作者机构：
  
  1.首都医科大学附属复兴医院，北京 100045
  2.陕西中医药大学第一附属医院，陕西咸阳 712046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231122
  CLC： R2-0;R22;R242;R2-031;R285.5
- Received：05 March 2023，
  
  Published Online：12 April 2023，
  
  Published：20 August 2023
- 稿件说明：
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许光远,张茁,张晓明.苦瓜提取物调节ZDF糖尿病大鼠糖异生的作用机制[J].中国实验方剂学杂志,2023,29(16):65-71.

XU Guangyuan,ZHANG Zhuo,ZHANG Xiaoming.Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):65-71.
许光远,张茁,张晓明.苦瓜提取物调节ZDF糖尿病大鼠糖异生的作用机制[J].中国实验方剂学杂志,2023,29(16):65-71. DOI： 10.13422/j.cnki.syfjx.20231122.

XU Guangyuan,ZHANG Zhuo,ZHANG Xiaoming.Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(16):65-71. DOI： 10.13422/j.cnki.syfjx.20231122.

摘要

目的

观察苦瓜提取物对糖尿病大鼠糖异生信号通路的影响。

方法

5~6周龄雄性Zucker Diabetic Fatty（ZDF）大鼠随机分为模型组、苦瓜组（苦瓜提取物0.40 g·kg

-1

灌胃），另7只健康雄性ZDF（fa/+）大鼠为正常组，每日1次灌胃，连续6周。实验过程中，观察大鼠一般情况，记录体质量，第1、3、5周检测空腹血糖、随机血糖；第6周行口服葡萄糖耐量实验（OGTT）、检测大鼠血清甘油三酯（TG）、游离脂肪酸（FFA）、总胆固醇（TC）、天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）；肝苏木素-伊红（HE）染色检测肝形态结构；肝糖原染色（PAS）检测肝糖原存储；采用实时荧光定量聚合酶链式反应（Real-time PCR）检测肝脏磷酸稀醇式丙酮酸羧激酶（PEPCK）、葡萄糖-6-磷酸酶（G6Pase）mRNA表达；蛋白免疫印迹法（Western blot）检测肝脏叉头转录因子1（FoxO1）磷酸化水平及磷酸稀醇式丙酮酸羧激酶（PEPCK）、G6Pase蛋白表达。

结果

与模型组比较，苦瓜组大鼠体质量、空腹血糖、随机血糖、糖耐量明显改善（

0.05，

0.01）；血清FFA、TC、TG明显降低（

0.05，

0.01）；ALT、AST各组间差异无统计学意义；HE显示肝细胞排列较整齐，脂肪样变性减轻；PAS显示肝糖原储存增加；肝p-FoxO1蛋白表达显著升高（

0.01），FoxO1蛋白表达无显著差异，PEPCK、G6Pase mRNA及蛋白表达明显降低（

0.05）。

结论

苦瓜提取物具有降糖、降脂、改善糖耐量及肝糖原储备作用，与其通过上调FoxO1磷酸化来抑制PEPCK、G6Pase表达，调控糖异生相关。

Abstract

Objective

To observe the effect of

Momordica charantia

extract （MCE） on the gluconeogenesis signaling pathway in diabetes rats.

Method

Male Zucker Diabetic Fatty （ZDF） rats aged 5-6 weeks were randomly divided into a model group and an MCE group （administered MCE at a dose of 0.40 g·kg

-1

by gavage）. Additionally， seven healthy male ZDF （fa/+） rats were assigned to the normal group and received administration once daily for six consecutive weeks. During the experiment， the general condition of the rats was observed， and body weight was recorded. Fasting blood glucose and random blood glucose levels were measured in the 1

， 3

， and 5

weeks. In the 6th week， an oral glucose tolerance test （OGTT） was conducted， and serum levels of triglycerides （TG）， free fatty acid （FFA）， total cholesterol （TC）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） were measured. Hematoxylin-eosin （HE） staining was performed to examine liver morphology， periodic acid-Schiff （PAS） staining was used to assess hepatic glycogen storage， and Real-time polymerase chain reaction （PCR） was employed to measure the mRNA expression of phosphoenolpyruvate carboxykinase （PEPCK） and glucose-6-phosphatase （G6Pase） in the liver. Western blot analysis was conducted to measure the phosphorylation level of forkhead box protein O1 （FoxO1） and the protein expression of PEPCK and G6Pase in the liver.

Result

Compared with the model group， the MCE group showed significant improvements in body weight， fasting blood glucose， random blood glucose， and glucose tolerance （

0.05，

0.01） and reduced serum levels of FFA， TC， and TG （

0.05，

0.01）. There were no significant differences in ALT and AST between the two groups. In the MCE group， the HE staining revealed more orderly liver cell arrangement and reduced hepatic steatosis and the PAS staining showed increased hepatic glycogen storage. The protein expression of p-FoxO1 in the liver was significantly elevated （

0.01）， while there was no significant difference in FoxO1 protein expression. The mRNA and protein expression of PEPCK and G6Pase significantly decreased （

0.05）.

Conclusion

MCE exhibits glucose-lowering and lipid-lowering effects， improves glucose tolerance， and enhances hepatic glycogen storage. These effects may be attributed to the upregulation of p-FoxO1， leading to the inhibition of PEPCK and G6Pase expression and the regulation of gluconeogenesis-related processes.

关键词

Keywords

references

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Mechanism of Momordica charantia Extract in Regulating Gluconeogenesis in ZDF Diabetes Rats

DOI：10.13422/j.cnki.syfjx.20231122

摘要

Abstract

关键词

Keywords

references