青钱柳对2型糖尿病大鼠血糖及肠道GLP-1分泌的影响

邹雅倩; 陈靓; 慕佳; 王雅靖; 陈絮蒙

doi:10.13386/j.issn1002-0306.2024040157

青钱柳对2型糖尿病大鼠血糖及肠道GLP-1分泌的影响

Effect of Cyclocarya paliurus on Glucose Metabolism and Intestinal GLP-1 Secretion in Type 2 Diabetic Rats

摘要

摘要: 目的：研究青钱柳对于2型糖尿病大鼠的降血糖作用及对肠道胰高血糖素样肽-1（glucagon-like peptide-1，GLP-1）分泌的影响，并初步探讨其作用机制。方法：高脂高糖饮食联合链脲佐菌素构建2型糖尿病大鼠模型，分别给予低剂量青钱柳（400 mg/kg）、高剂量青钱柳（800 mg/kg）以及二甲双胍（150 mg/kg），连续灌胃给药8周，每周称量大鼠体质量，记录摄食量，测定空腹血糖值。给药8周后，进行口服糖耐量试验。测定大鼠血清中糖化血红蛋白百分含量、空腹胰岛素、GLP-1、谷丙转氨酶、谷草转氨酶水平及肝脏组织中糖原水平、葡萄糖激酶（glucokinase，GK）活性；HE染色法观察大鼠肝脏病理学变化；Real-time PCR法检测结肠组织中GCG、PC1/3及肝脏组织中GK mRNA表达的相对量；免疫组化法检测结肠组织中GLP-1的蛋白表达。结果：与模型组相比，青钱柳低、高剂量组可有效控制大鼠摄食量，稳定体质量，正向调节T2DM动物基本状态；青钱柳低、高剂量组大鼠糖化血红蛋白百分含量、胰岛素抵抗指数水平均极显著低于模型组（P<0.01），青钱柳高剂量组大鼠空腹胰岛素水平极显著低于模型组（P<0.01），胰岛素敏感指数水平则显著高于模型组（P<0.05）；HE染色结果表明，青钱柳可有效改善2型糖尿病引起的肝脏病理损伤；肝脏及结肠组织免疫组化及Real-time PCR结果表明，青钱柳可显著提高循环及结肠组织中GLP-1表达及分泌水平（P<0.05，P<0.01），提高肝脏GK活性及mRNA表达，恢复肝糖原水平（P<0.05，P<0.01）。结论：青钱柳可有效稳定血糖、改善胰岛素抵抗并调节GLP-1合成与分泌，对肝脏有一定保护作用，其机制涉及肝肠轴调节。

Abstract: Objective: This study aimed to evaluate the hypoglycemic effect of Cyclocarya paliurus on type 2 diabetic rats and its impact on glucagon-like peptide-1 (GLP-1) secretion, and to preliminarily explore its mechanism. Methods: Type 2 diabetes was induced in rats using a high-fat, high-sugar diet combined with streptozotocin. Rats were then treated with low-dose (400 mg/kg) and high-dose (800 mg/kg) Cyclocarya paliurus, or metformin (150 mg/kg), via gavage for 8 weeks. Weekly assessments included body weight, food intake, and fasting glucose levels. After 8 weeks, an oral glucose tolerance test was conducted. Serum levels of glycated hemoglobin, fasting insulin, GLP-1, alanine aminotransferase, and aspartate aminotransferase were measured. Liver glycogen levels and glucokinase (GK) activity were assessed, and liver pathology was examined using HE staining. Real-time PCR analyzed mRNA expression of GCG, PC1/3 in colon tissues, and GK in liver tissues, while immunohistochemistry was used to detect GLP-1 protein expression in colon tissues. Results: Cyclocarya paliurus treatment (both low- and high-doses) effectively reduced food intake and stabilized body weight in diabetic rats, positively influencing their diabetes condition compared to the model group. Glycated hemoglobin and the insulin resistance index were significantly lower (P<0.01) in both low- and high-doses Cyclocarya paliurus-treated rats. Fasting insulin was significantly lower (P<0.01), while the insulin sensitivity index was significantly higher in the high-dose group than that in the model group (P<0.05). HE staining revealed improved liver pathology in Cyclocarya paliurus-treated groups. Immunohistochemistry and Real-time PCR results indicated increased GLP-1 expression and secretion in both circulating blood and colon tissues (P<0.05, P<0.01) and enhanced activity and mRNA expression of GK in liver (P<0.01). Additionally, hepatic glycogen levels were elevated (P<0.05, P<0.01). Conclusion: Cyclocarya paliurus could effectively stabilize blood glucose levels, improve insulin resistance, and regulate GLP-1 synthesis and secretion, which has a certain protective effect on the liver. These effects are mediated through the regulation of the liver-intestinal axis.