Objective: To elucidate the effect of Huanglian-Renshen-Decoction(HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β-cell identity through regulating paracrine and endocrine glucagon-like peptide-1(...Objective: To elucidate the effect of Huanglian-Renshen-Decoction(HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β-cell identity through regulating paracrine and endocrine glucagon-like peptide-1(GLP-1)/GLP-1 receptor(GLP-1R) in both islet and intestine. Methods: The db/db mice were divided into the model(distilled water), low-dose HRD(LHRD, 3 g/kg), high-dose HRD(HHRD, 6 g/kg), and liraglutide(400 μg/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group(n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry(IHC) and immunofluorescence(IF) staining. Then,GLP-1, GLP-1R, prohormone convertase 1/3(PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A(MafA), and pancreatic and duodenal homeobox 1(PDX1) were detected by Western blot, IHC,IF, and real-time quantitative polymerase chain reaction, respectively. Results: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time(P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon(P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass(P<0.01). After HRD treatment, the levels of GLP-1,GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased(P<0.05 or P<0.01).Conclusion: HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.展开更多
基金Supported by the National Natural Science Foundation of China(No.82004358)。
文摘Objective: To elucidate the effect of Huanglian-Renshen-Decoction(HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β-cell identity through regulating paracrine and endocrine glucagon-like peptide-1(GLP-1)/GLP-1 receptor(GLP-1R) in both islet and intestine. Methods: The db/db mice were divided into the model(distilled water), low-dose HRD(LHRD, 3 g/kg), high-dose HRD(HHRD, 6 g/kg), and liraglutide(400 μg/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group(n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry(IHC) and immunofluorescence(IF) staining. Then,GLP-1, GLP-1R, prohormone convertase 1/3(PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A(MafA), and pancreatic and duodenal homeobox 1(PDX1) were detected by Western blot, IHC,IF, and real-time quantitative polymerase chain reaction, respectively. Results: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time(P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon(P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass(P<0.01). After HRD treatment, the levels of GLP-1,GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased(P<0.05 or P<0.01).Conclusion: HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
