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Cited 46 times in

Pyruvate inhibits zinc-mediated pancreatic islet cell death and diabetes

DC FieldValueLanguage
dc.contributor.author장인익-
dc.date.accessioned2015-07-15T17:20:10Z-
dc.date.available2015-07-15T17:20:10Z-
dc.date.issued2003-
dc.identifier.issn0012-186X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/114699-
dc.description.abstractAIMS/HYPOTHESIS: We have shown that zinc ion (Zn2+) in secretory granules of pancreatic beta cells could act as a paracrine death effector in streptozotocin-induced diabetes. As Zn2+ has been reported to perturb glycolysis, we studied if pyruvate could inhibit Zn(2+)-mediated islet cell death in vitro and streptozotocin-induced diabetes in vivo by normalizing intracellular energy metabolism. METHODS: Cell death was measured by quantitative viable cell staining and Hoechst/propidium iodide staining. ATP was measured by bioluminescence determination. Pyruvate was infused through the tail vein 1 h before streptozotocin administration. Beta-cell volume was measured by point counting of the insulin-containing cells. RESULTS: Zn2+ induced classical necrosis on MIN6N8 insulinoma cells which was associated with a rapid decline of intracellular ATP levels. Pyruvate inhibited Zn(2+)-induced necrosis of insulinoma cells and depletion of intracellular ATP by Zn2+. Pyruvate did not inhibit other types of necrosis or apoptosis. Energy substrates such as oxaloacetate, alpha-ketoglutarate and succinic acid dimethylester also attenuated Zn(2+)-induced insulinoma cell death. Methylpyruvate that does not generate NAD+ in the cytoplasm or alpha-ketoisocaproate that stimulates ATP generation exclusively in mitochondria also protected insulinoma cells from Zn(2+)-induced necrosis. Pyruvate infusion inhibited the development of diabetes by protecting beta-cell mass after streptozotocin administration. CONCLUSION/INTERPRETATION: These results indicate that pyruvate inhibits Zn(2+)-induced necrosis of beta cells in vitro by protecting intracellular ATP levels and also streptozotocin-induced diabetes in vivo where Zn2+ has been reported to act as a paracrine death effector-
dc.description.statementOfResponsibilityopen-
dc.format.extent1220~1227-
dc.relation.isPartOfDiabetologia-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titlePyruvate inhibits zinc-mediated pancreatic islet cell death and diabetes-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학)-
dc.contributor.googleauthorI. Chang-
dc.contributor.googleauthorN. Cho-
dc.contributor.googleauthorM.-S. Lee-
dc.contributor.googleauthorJ.-Y. Koh-
dc.identifier.doi10.1007/s00125-003-1171-z-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03461-
dc.relation.journalcodeJ00727-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs00125-003-1171-z-
dc.contributor.alternativeNameChang, In Ik-
dc.contributor.affiliatedAuthorChang, In Ik-
dc.rights.accessRightsnot free-
dc.citation.volume46-
dc.citation.number9-
dc.citation.startPage1220-
dc.citation.endPage1227-
dc.identifier.bibliographicCitationDiabetologia, Vol.46(9) : 1220-1227, 2003-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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