The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation

Ginsenoside Rb1 has been shown to have antidiabetic and anti-inflammatory effects. Its major metabolite, compound K (CK), can stimulate the secretion of glucagon-like peptide-1 (GLP1), a gastrointestinal hormone that plays a vital role in regulating glucose metabolism. However, the mechanism underly...

Full description

Bibliographic Details
Main Authors: Fengyuan Tian, Xi Wang, Haixiang Ni, Xiaohong Feng, Xiao Yuan, Qi Huang
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:Journal of Pharmacological Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861320301110
_version_ 1818383574672343040
author Fengyuan Tian
Xi Wang
Haixiang Ni
Xiaohong Feng
Xiao Yuan
Qi Huang
author_facet Fengyuan Tian
Xi Wang
Haixiang Ni
Xiaohong Feng
Xiao Yuan
Qi Huang
author_sort Fengyuan Tian
collection DOAJ
description Ginsenoside Rb1 has been shown to have antidiabetic and anti-inflammatory effects. Its major metabolite, compound K (CK), can stimulate the secretion of glucagon-like peptide-1 (GLP1), a gastrointestinal hormone that plays a vital role in regulating glucose metabolism. However, the mechanism underlying the regulation of GLP1 secretion by compound K has not been fully explored. This study was designed to investigate whether CK ameliorates incretin impairment by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation in NCI–H716 cells. Using NCI–H716 cells as a model cell line for GLP1 secretion, we analyzed the effect of CK on the expression of RhoA/ROCK/YAP pathway components. Our results suggest that the effect of CK on GLP1 secretion depends on the anti-inflammatory effect of CK. We also demonstrated that CK can affect the RhoA/ROCK/YAP pathway, which is downstream of transforming growth factor β1 (TGFβ1), by maintaining the capacity of intestinal differentiation. In addition, this effect was mediated by regulating F/G-actin dynamics. These results provide not only the mechanistic insight for the effect of CK on intestinal L cells but also the molecular basis for the further development of CK as a potential therapeutic agent to treat type 2 diabetes mellitus (T2D).
first_indexed 2024-12-14T03:08:32Z
format Article
id doaj.art-170cb06c877e4d35b78a828f9508a2f7
institution Directory Open Access Journal
issn 1347-8613
language English
last_indexed 2024-12-14T03:08:32Z
publishDate 2021-01-01
publisher Elsevier
record_format Article
series Journal of Pharmacological Sciences
spelling doaj.art-170cb06c877e4d35b78a828f9508a2f72022-12-21T23:19:19ZengElsevierJournal of Pharmacological Sciences1347-86132021-01-0114518896The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formationFengyuan Tian0Xi Wang1Haixiang Ni2Xiaohong Feng3Xiao Yuan4Qi Huang5Department of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR ChinaCentral Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR ChinaDepartment of Endocrinology, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310006, PR China; Corresponding author. Fax: +86 574 87068200.Ginsenoside Rb1 has been shown to have antidiabetic and anti-inflammatory effects. Its major metabolite, compound K (CK), can stimulate the secretion of glucagon-like peptide-1 (GLP1), a gastrointestinal hormone that plays a vital role in regulating glucose metabolism. However, the mechanism underlying the regulation of GLP1 secretion by compound K has not been fully explored. This study was designed to investigate whether CK ameliorates incretin impairment by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation in NCI–H716 cells. Using NCI–H716 cells as a model cell line for GLP1 secretion, we analyzed the effect of CK on the expression of RhoA/ROCK/YAP pathway components. Our results suggest that the effect of CK on GLP1 secretion depends on the anti-inflammatory effect of CK. We also demonstrated that CK can affect the RhoA/ROCK/YAP pathway, which is downstream of transforming growth factor β1 (TGFβ1), by maintaining the capacity of intestinal differentiation. In addition, this effect was mediated by regulating F/G-actin dynamics. These results provide not only the mechanistic insight for the effect of CK on intestinal L cells but also the molecular basis for the further development of CK as a potential therapeutic agent to treat type 2 diabetes mellitus (T2D).http://www.sciencedirect.com/science/article/pii/S1347861320301110Compound KGlucagon-like peptide-1 (GLP1)NCI–H716 cell lineCytoskeletonDiabetes
spellingShingle Fengyuan Tian
Xi Wang
Haixiang Ni
Xiaohong Feng
Xiao Yuan
Qi Huang
The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
Journal of Pharmacological Sciences
Compound K
Glucagon-like peptide-1 (GLP1)
NCI–H716 cell line
Cytoskeleton
Diabetes
title The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
title_full The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
title_fullStr The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
title_full_unstemmed The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
title_short The ginsenoside metabolite compound K stimulates glucagon-like peptide-1 secretion in NCI–H716 cells by regulating the RhoA/ROCKs/YAP signaling pathway and cytoskeleton formation
title_sort ginsenoside metabolite compound k stimulates glucagon like peptide 1 secretion in nci h716 cells by regulating the rhoa rocks yap signaling pathway and cytoskeleton formation
topic Compound K
Glucagon-like peptide-1 (GLP1)
NCI–H716 cell line
Cytoskeleton
Diabetes
url http://www.sciencedirect.com/science/article/pii/S1347861320301110
work_keys_str_mv AT fengyuantian theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiwang theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT haixiangni theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiaohongfeng theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiaoyuan theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT qihuang theginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT fengyuantian ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiwang ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT haixiangni ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiaohongfeng ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT xiaoyuan ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation
AT qihuang ginsenosidemetabolitecompoundkstimulatesglucagonlikepeptide1secretioninncih716cellsbyregulatingtherhoarocksyapsignalingpathwayandcytoskeletonformation