Compound 19e, a Novel Glucokinase Activator, Protects against Cytokine-Induced Beta-Cell Apoptosis in INS-1 Cells
DC Field | Value | Language |
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dc.contributor.author | Oh, Yoon Sin | - |
dc.contributor.author | Seo, Eunhui | - |
dc.contributor.author | Park, Kaapjoo | - |
dc.contributor.author | Jun, Hee-Sook | - |
dc.date.available | 2020-02-27T19:42:07Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-03 | - |
dc.identifier.issn | 1663-9812 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6302 | - |
dc.description.abstract | Previously, compound 19e, a novel heteroaryl-containing benzamide derivative, was identified as a potent glucokinase activator (GKA) and showed a glucose-lowering effect in diabetic mice. In this study, the anti-apoptotic actions of 19e were evaluated in INS-1 pancreatic beta-cells co-treated with TNF-alpha and IL-1 beta to induce cell death. Compound 19e protected INS-1 cells from cytokine-induced cell death, and the effect was similar to treatment with another GKA or exendin-4. Compound 19e reduced annexin-V stained cells and the expression of cleaved caspase-3 and poly (ADP-ribose) polymerase protein, as well as upregulated the expression of B-cell lymphoma-2 protein. Compound 19e inhibited apoptotic signaling via induction of the ATP content, and the effect was correlated with the downregulation of nuclear factor-kappa B p65 and inducible nitric oxide synthase. Further, 19e increased NAD-dependent protein deacetylase sirtuin-1 (SIRT1) deacetylase activity, and the anti-apoptotic effect of 19e was attenuated by SIRT1 inhibitor or SIRT1 siRNA treatment. Our results demonstrate that the novel GKA, 19e, prevents cytokine-induced beta-cell apoptosis via SIRT1 activation and has potential as a therapeutic drug for the preservation of pancreatic beta-cells. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.relation.isPartOf | FRONTIERS IN PHARMACOLOGY | - |
dc.title | Compound 19e, a Novel Glucokinase Activator, Protects against Cytokine-Induced Beta-Cell Apoptosis in INS-1 Cells | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000397556700001 | - |
dc.identifier.doi | 10.3389/fphar.2017.00169 | - |
dc.identifier.bibliographicCitation | FRONTIERS IN PHARMACOLOGY, v.8 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85018625100 | - |
dc.citation.title | FRONTIERS IN PHARMACOLOGY | - |
dc.citation.volume | 8 | - |
dc.contributor.affiliatedAuthor | Oh, Yoon Sin | - |
dc.contributor.affiliatedAuthor | Seo, Eunhui | - |
dc.contributor.affiliatedAuthor | Jun, Hee-Sook | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | compound 19e | - |
dc.subject.keywordAuthor | glucokinase activator | - |
dc.subject.keywordAuthor | beta-cell | - |
dc.subject.keywordAuthor | apoptosis | - |
dc.subject.keywordAuthor | cytokine | - |
dc.subject.keywordAuthor | NAD-dependent protein | - |
dc.subject.keywordAuthor | deacetylase sirtuin-1 | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | TYPE-2 DIABETES-MELLITUS | - |
dc.subject.keywordPlus | GLUCAGON-LIKE PEPTIDE-1 | - |
dc.subject.keywordPlus | INTERLEUKIN-1-BETA-INDUCED APOPTOSIS | - |
dc.subject.keywordPlus | ER STRESS | - |
dc.subject.keywordPlus | TNF-ALPHA | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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