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

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.