Treatment with glucokinase activator, YH-GKA, increases cell proliferation and decreases glucotoxic apoptosis in INS-1 cells
DC Field | Value | Language |
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dc.contributor.author | Oh, Yoon Sin | - |
dc.contributor.author | Lee, Youn-Jung | - |
dc.contributor.author | Park, Kaapjoo | - |
dc.contributor.author | Choi, Hyun Ho | - |
dc.contributor.author | Yoo, Sangjong | - |
dc.contributor.author | Jun, Hee-Sook | - |
dc.date.available | 2020-02-28T18:42:51Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2014-01-23 | - |
dc.identifier.issn | 0928-0987 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/12890 | - |
dc.description.abstract | Glucokinase (GK), an enzyme that phosphorylates glucose to form glucose-6-phosphate, has a role in regulating insulin secretion and proliferation in beta cells. GK activators (GKAs) have been developed as new therapies for type 2 diabetes. In this study, we evaluated the proliferation and anti-apoptotic actions of YH-GKA, a novel and potent GKA, in INS-1 pancreatic beta-cells. YH-GKA treatment increased cell numbers at 3 mM glucose via upregulation of insulin receptor substrate-2 and subsequent activation of AKT/protein kinase B phosphorylation. YH-GKA also increased beta-catenin and cyclin D2 mRNA expression and inactivated GSK3 beta by increasing phosphorylation. These proliferative effects of YH-GKA were attenuated by IRS-2 downregulation. Moreover, YH-GKA reduced annexin-V-stained cells and expression levels of cleaved poly (ADP-ribose) polymerase and caspase-3 induced by glucotoxicity. YH-GKA inhibited apoptotic signaling via induction of ATP content, mitochondrial membrane potential, and citrate synthase activity and was correlated with changes of the mitochondrial function-related genes. YH-GKA also increased interaction between GK and voltage-dependent anion-selective channel protein. Our results suggest that the novel GKA, YH-GKA, promotes beta cell growth and prevents glucotoxic beta cell apoptosis. Therefore, YH-GKA may provide a therapy that compensates for beta cell loss in patients with type 2 diabetes. (C) 2013 Elsevier B.V. All rights reserved. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.relation.isPartOf | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | - |
dc.subject | PANCREATIC BETA-CELLS | - |
dc.subject | MITOCHONDRIAL DYSFUNCTION | - |
dc.subject | SIGNAL-TRANSDUCTION | - |
dc.subject | DIABETES-MELLITUS | - |
dc.subject | DOWN-REGULATION | - |
dc.subject | RECEPTOR | - |
dc.subject | GLUCOSE | - |
dc.subject | GROWTH | - |
dc.subject | IRS-2 | - |
dc.subject | MECHANISMS | - |
dc.title | Treatment with glucokinase activator, YH-GKA, increases cell proliferation and decreases glucotoxic apoptosis in INS-1 cells | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000328872200016 | - |
dc.identifier.doi | 10.1016/j.ejps.2013.09.005 | - |
dc.identifier.bibliographicCitation | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, v.51, pp.137 - 145 | - |
dc.identifier.scopusid | 2-s2.0-84885737056 | - |
dc.citation.endPage | 145 | - |
dc.citation.startPage | 137 | - |
dc.citation.title | EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | - |
dc.citation.volume | 51 | - |
dc.contributor.affiliatedAuthor | Oh, Yoon Sin | - |
dc.contributor.affiliatedAuthor | Lee, Youn-Jung | - |
dc.contributor.affiliatedAuthor | Yoo, Sangjong | - |
dc.contributor.affiliatedAuthor | Jun, Hee-Sook | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Glucokinase activator | - |
dc.subject.keywordAuthor | Beta-cell proliferation | - |
dc.subject.keywordAuthor | Glucotoxicity | - |
dc.subject.keywordAuthor | INS-1 cells | - |
dc.subject.keywordAuthor | Type 2 diabetes | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordPlus | PANCREATIC BETA-CELLS | - |
dc.subject.keywordPlus | MITOCHONDRIAL DYSFUNCTION | - |
dc.subject.keywordPlus | SIGNAL-TRANSDUCTION | - |
dc.subject.keywordPlus | DIABETES-MELLITUS | - |
dc.subject.keywordPlus | DOWN-REGULATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | GLUCOSE | - |
dc.subject.keywordPlus | GROWTH | - |
dc.subject.keywordPlus | IRS-2 | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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