Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장유진 | - |
dc.date.accessioned | 2016-08-27T04:08:20Z | - |
dc.date.available | 2016-08-27T04:08:20Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.issn | 1532-8600 | - |
dc.identifier.other | OAK-14755 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/217118 | - |
dc.description.abstract | Objective. Ezetimibe is known as a Niemann-Pick C1-Like 1 (NPC1L1) inhibitor and has been used as an agent for hypercholesterolemia. In our previous study, ezetimibe administration improved glycemic control and increased glucagon like peptide-1 (GLP-1), an incretin hormone with anti-diabetic properties. However, the mechanisms by which ezetimibe stimulates GLP-1 secretion are not fully understood. Thus, the specific aim of this study was to investigate the mechanism(s) by which ezetimibe stimulates GLP-1 secretion. Materials/methods. Male KK/H1J mice were divided into following groups: AIN-93G (NC), NC with ezetimibe (10 mg/kg/day), 45% high fat (HF) diet, and HF diet with ezetimibe. To investigate the role of ezetimibe in glucose homeostasis and GLP-1 secretion, an insulin tolerance test was performed and serum and intestinal GLP-1 levels and intestinal mRNA expression involved in GLP-1 synthesis were measured after 6 weeks of ezetimibe treatment. In vivo and in vitro dipeptidyl peptidase-4 (DPP-4) inhibition assays were employed to demonstrate the association between ezetimibe-induced GLP-1 change and DPP-4. The molecular mechanism by which ezetimibe affects GLP-1 secretion was evaluated by using human enteroendoctine NCI-H716 cells. Results. Ezetimibe supplementation significantly ameliorated HF-increased glucose and insulin resistance in the type 2 diabetic KK/H1J mouse model. Serum and intestinal active GLP-1 levels were significantly increased by ezetimibe in HF-fed animals. However, mRNA expression of genes involved in intestinal GLP-1 synthesis was not altered. Furthermore, ezetimibe did not inhibit the activity of either in vivo or in vitro dipeptidyl peptidase-4 (DPP-4). The direct effects of ezetimibe on GLP-1 secretion and L cell secretory mechanisms were examined in human NCI-H716 intestinal cells. Ezetimibe significantly stimulated active GLP-1 secretion, which was accompanied by the activation of mitogen-activated Protein/extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK). Ezetimibe-increased GLP-1 secretion was abrogated by inhibiting the MEK/ERK pathway with PD98059. Conclusion. These findings suggest a possible novel biological role of ezetimibe in glycemic control to stimulate intestinal GLP-1 secretion via the MEK/ERK signaling pathway. (C) 2015 Published by Elsevier Inc. | - |
dc.language | English | - |
dc.publisher | W B SAUNDERS CO-ELSEVIER INC | - |
dc.subject | Ezetimibe | - |
dc.subject | GLP-1 | - |
dc.subject | DPP-4 | - |
dc.subject | ERK | - |
dc.subject | MEK | - |
dc.title | Ezetimibe Stimulates Intestinal Glucagon-Like Peptide 1 Secretion Via the MEK/ERK Pathway Rather Than Dipeptidyl Peptidase 4 Inhibition | - |
dc.type | Article | - |
dc.relation.issue | 5 | - |
dc.relation.volume | 64 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 633 | - |
dc.relation.lastpage | 641 | - |
dc.relation.journaltitle | METABOLISM-CLINICAL AND EXPERIMENTAL | - |
dc.identifier.doi | 10.1016/j.metabol.2015.02.001 | - |
dc.identifier.wosid | WOS:000352253300009 | - |
dc.author.google | Chang, Eugene | - |
dc.author.google | Kim, Lisa | - |
dc.author.google | Choi, Jung Mook | - |
dc.author.google | Park, Se Eun | - |
dc.author.google | Rhee, Eun-Jung | - |
dc.author.google | Lee, Won-Young | - |
dc.author.google | Oh, Ki-Won | - |
dc.author.google | Park, Sung-Woo | - |
dc.author.google | Park, Dong Il | - |
dc.author.google | Park, Cheol-Young | - |
dc.contributor.scopusid | 장유진(30367468300) | - |
dc.date.modifydate | 20230411105300 | - |