21 99

Cited 0 times in

DA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice

DC Field Value Language
dc.contributor.author강은석-
dc.contributor.author왕혜진-
dc.contributor.author이향규-
dc.date.accessioned2022-05-09T17:07:14Z-
dc.date.available2022-05-09T17:07:14Z-
dc.date.issued2022-03-
dc.identifier.issn2233-6079-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/188386-
dc.description.abstractBackground: We investigated the antidiabetic effects of DA-1241, a novel G protein-coupled receptor (GPR) 119 agonist, in vitro and in vivo. Methods: DA-1241 was administrated to high-fat diet (HFD)-fed C57BL/6J mice for 12 weeks after hyperglycaemia developed. Oral/intraperitoneal glucose tolerance test and insulin tolerance test were performed. Serum insulin and glucagon-like peptide-1 (GLP-1) levels were measured during oral glucose tolerance test. Insulinoma cell line (INS-1E) cells and mouse islets were used to find whether DA-1241 directly stimulate insulin secretion in beta cell. HepG2 cells were used to evaluate the gluconeogenesis and autophagic process. Autophagic flux was evaluated by transfecting microtubule-associated protein 1 light chain 3-fused to green fluorescent protein and monomeric red fluorescent (mRFP-GFP-LC3) expression vector to HepG2 cells. Results: Although DA-1241 treatment did not affect body weight gain and amount of food intake, fasting blood glucose level decreased along with increase in GLP-1 level. DA-1241 improved only oral glucose tolerance test and showed no effect in intraperitoneal glucose tolerance test. No significant effect was observed in insulin tolerance test. DA-1241 did not increase insulin secretion in INS-1E cell and mouse islets. DA-1241 reduced triglyceride content in the liver thereby improved fatty liver. Additionally, DA-1241 reduced gluconeogenic enzyme expression in HepG2 cells and mouse liver. DA-1241 reduced autophagic flow in HepG2 cells. Conclusion: These findings suggested that DA-1241 augmented glucose-dependent insulin release via stimulation of GLP-1 secretion, and reduced hepatic gluconeogenesis, which might be associated with autophagic blockage, leading to improved glycaemic control.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherKorean Diabetes Association-
dc.relation.isPartOfDIABETES & METABOLISM JOURNAL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHBlood Glucose / metabolism-
dc.subject.MESHDiabetes Mellitus, Experimental* / drug therapy-
dc.subject.MESHDiabetes Mellitus, Experimental* / metabolism-
dc.subject.MESHGlucagon-Like Peptide 1-
dc.subject.MESHGluconeogenesis-
dc.subject.MESHHyperglycemia* / drug therapy-
dc.subject.MESHHyperglycemia* / metabolism-
dc.subject.MESHInsulin-
dc.subject.MESHInsulin Secretion-
dc.subject.MESHLiver / metabolism-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.titleDA-1241, a Novel GPR119 Agonist, Improves Hyperglycaemia by Inhibiting Hepatic Gluconeogenesis and Enhancing Insulin Secretion in Diabetic Mice-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorYoujin Kim-
dc.contributor.googleauthorSi Woo Lee-
dc.contributor.googleauthorHyejin Wang-
dc.contributor.googleauthorRyeong-Hyeon Kim-
dc.contributor.googleauthorHyun Ki Park-
dc.contributor.googleauthorHangkyu Lee-
dc.contributor.googleauthorEun Seok Kang-
dc.identifier.doi10.4093/dmj.2021.0056-
dc.contributor.localIdA00068-
dc.contributor.localIdA02422-
dc.contributor.localIdA03282-
dc.relation.journalcodeJ00720-
dc.identifier.eissn2233-6087-
dc.identifier.pmid35052026-
dc.subject.keywordAutophagy-
dc.subject.keywordG protein-coupled receptor-
dc.subject.keywordGlucagon-like peptide 1-
dc.subject.keywordGluconeogenesis-
dc.subject.keywordInsulin secretion-
dc.contributor.alternativeNameKang, Eun Seok-
dc.contributor.affiliatedAuthor강은석-
dc.contributor.affiliatedAuthor왕혜진-
dc.contributor.affiliatedAuthor이향규-
dc.citation.volume46-
dc.citation.number2-
dc.citation.startPage337-
dc.citation.endPage348-
dc.identifier.bibliographicCitationDIABETES & METABOLISM JOURNAL, Vol.46(2) : 337-348, 2022-03-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
3. College of Nursing (간호대학) > Dept. of Nursing (간호학과) > 1. Journal Papers

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.