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:	Ma L, Cao X, Ye X, Ye J, Sun Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	sennoside a glucagon-like peptide-1 (glp-1) extracellular signal-regulated kinases 1/2 (erk1/2) l-cells prohormone convertase 1/3 (pc1/3) Specialties of internal medicine RC581-951
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spelling	oai:doaj.org-article:fe5bc8eadbe14807b451beed844f55b92021-12-02T09:18:32ZSennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells1178-7007https://doaj.org/article/fe5bc8eadbe14807b451beed844f55b92020-04-01T00:00:00Zhttps://www.dovepress.com/sennoside-a-induces-glp-1-secretion-through-activation-of-the-erk12-pa-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Li 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, PC1/3Ma LCao XYe XYe JSun YDove Medical Pressarticlesennoside aglucagon-like peptide-1 (glp-1)extracellular signal-regulated kinases 1/2 (erk1/2)l-cellsprohormone convertase 1/3 (pc1/3)Specialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 1407-1415 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	sennoside a glucagon-like peptide-1 (glp-1) extracellular signal-regulated kinases 1/2 (erk1/2) l-cells prohormone convertase 1/3 (pc1/3) Specialties of internal medicine RC581-951
spellingShingle	sennoside a glucagon-like peptide-1 (glp-1) extracellular signal-regulated kinases 1/2 (erk1/2) l-cells prohormone convertase 1/3 (pc1/3) Specialties of internal medicine RC581-951 Ma L Cao X Ye X Ye J Sun Y Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
description	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
format	article
author	Ma L Cao X Ye X Ye J Sun Y
author_facet	Ma L Cao X Ye X Ye J Sun Y
author_sort	Ma L
title	Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
title_short	Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
title_full	Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
title_fullStr	Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
title_full_unstemmed	Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells
title_sort	sennoside a induces glp-1 secretion through activation of the erk1/2 pathway in l-cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/fe5bc8eadbe14807b451beed844f55b9
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_version_	1718398221368164352

Sennoside A Induces GLP-1 Secretion Through Activation of the ERK1/2 Pathway in L-Cells

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