Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
Li Ma,1 Xinyu Cao,2 Xiaotong Ye,2 Jianping Ye,2 Yongning Sun1,3 1Department of Traditional Chinese Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 2Shanghai Diabetes Institute, Shanghai Jiao Tong University...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2020
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| Acceso en línea: | https://doaj.org/article/fe5bc8eadbe14807b451beed844f55b9 |
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| Sumario: | Li Ma,1 Xinyu Cao,2 Xiaotong Ye,2 Jianping Ye,2 Yongning Sun1,3 1Department of Traditional Chinese Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 2Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 201306, People’s Republic of China; 3Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, People’s Republic of ChinaCorrespondence: Yongning Sun; Jianping Ye Tel +86-18930177579; +86-13818929364Email ynsun2002@126.com; yejianping@sjtu.edu.cnPurpose: Glucagon-like peptide-1 (GLP-1) is secreted from the intestinal L-cells to stimulate insulin secretion in the blood glucose control. Our previous study indicates that Sennoside A (SA) can increase the plasma GLP-1 level in a mouse model of type 2 diabetes. However, the mechanism of SA activity remains largely unknown. This issue was explored in this study.Materials and Methods: C57BL/6 mice were randomly divided into four groups: a control group without drug treatment, and the other groups with different SA dosages, respectively. Blood glucose was assayed by oral glucose tolerance test (OGTT). Plasma GLP-1 and insulin were investigated. Colon tissues were collected for mRNA or Western blot analysis. Immunofluorescence staining assays were performed to evaluate the number of β-cells and L-cells. In NCI-H716 cells, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors were employed to investigate the SA-induced GLP-1 secretion mechanism.Results: In this work, the SA was found to improve OGTT in mice. Plasma GLP-1 and insulin were markedly elevated by SA at the dosage of 45 mg/kg/day. Meanwhile, the increased phosphorylation status of EKR1/2 and prohormone convertase 1/3 (PC1/3) proteins were observed in the colon of SA-treated mice. The number of L-cells exhibited no change in each group. In the NCI-H716 cells, GLP-1 secretion induced by SA was blocked by the ERK1/2 inhibitor.Conclusion: The present study provides a direct evidence for the interaction between SA and L cells for induction of GLP-1 secretion. These data suggest that GLP-1 secretion induced by SA is dependent on the ERK1/2 signaling pathway. Therefore, the SA is a new drug candidate for the type 2 diabetes treatment by induction of GLP-1 secretion.Keywords: Sennoside A, glucagon-like peptide, 1, GLP, 1, extracellular signal-regulated kinases 1/2, ERK1/2, L-cells, prohormone convertase 1/3, PC1/3 |
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