Cited 36 times in
A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion
DC Field | Value | Language |
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dc.contributor.author | 강은석 | - |
dc.contributor.author | 김유선 | - |
dc.contributor.author | 김인숙 | - |
dc.contributor.author | 김철훈 | - |
dc.contributor.author | 안철우 | - |
dc.contributor.author | 이현철 | - |
dc.contributor.author | 임영신 | - |
dc.contributor.author | 차봉수 | - |
dc.date.accessioned | 2014-12-20T16:35:35Z | - |
dc.date.available | 2014-12-20T16:35:35Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 1470-269X | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/93008 | - |
dc.description.abstract | SLC30A8 encodes the β-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 191~198 | - |
dc.relation.isPartOf | PHARMACOGENOMICS JOURNAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Alleles | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Biomarkers, Pharmacological | - |
dc.subject.MESH | Calcineurin Inhibitors | - |
dc.subject.MESH | Cation Transport Proteins/genetics* | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Cyclosporine/adverse effects* | - |
dc.subject.MESH | Cyclosporine/therapeutic use | - |
dc.subject.MESH | Diabetes Mellitus/etiology* | - |
dc.subject.MESH | Diabetes Mellitus/genetics* | - |
dc.subject.MESH | Glucose/metabolism | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Immunosuppressive Agents/adverse effects | - |
dc.subject.MESH | Insulin/secretion* | - |
dc.subject.MESH | Intracellular Signaling Peptides and Proteins/genetics | - |
dc.subject.MESH | Intracellular Signaling Peptides and Proteins/metabolism | - |
dc.subject.MESH | Kidney Transplantation/adverse effects* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Muscle Proteins/genetics | - |
dc.subject.MESH | Muscle Proteins/metabolism | - |
dc.subject.MESH | Mutation | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Zinc Transporter 8 | - |
dc.title | A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Surgery (외과학) | - |
dc.contributor.googleauthor | I Kim | - |
dc.contributor.googleauthor | E S Kang | - |
dc.contributor.googleauthor | Y S Yim | - |
dc.contributor.googleauthor | S J Ko | - |
dc.contributor.googleauthor | S-H Jeong | - |
dc.contributor.googleauthor | J H Rim | - |
dc.contributor.googleauthor | Y S Kim | - |
dc.contributor.googleauthor | C W Ahn | - |
dc.contributor.googleauthor | B S Cha | - |
dc.contributor.googleauthor | H C Lee | - |
dc.contributor.googleauthor | C H Kim | - |
dc.identifier.doi | 10.1038/tpj.2010.22 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00068 | - |
dc.contributor.localId | A00785 | - |
dc.contributor.localId | A01057 | - |
dc.contributor.localId | A02270 | - |
dc.contributor.localId | A03301 | - |
dc.contributor.localId | A03385 | - |
dc.contributor.localId | A03996 | - |
dc.contributor.localId | A00842 | - |
dc.relation.journalcode | J02508 | - |
dc.identifier.eissn | 1473-1150 | - |
dc.identifier.pmid | 20351753 | - |
dc.identifier.url | http://www.nature.com/tpj/journal/v11/n3/full/tpj201022a.html | - |
dc.contributor.alternativeName | Kang, Eun Seok | - |
dc.contributor.alternativeName | Kim, Yu Seun | - |
dc.contributor.alternativeName | Kim, In Sook | - |
dc.contributor.alternativeName | Kim, Chul Hoon | - |
dc.contributor.alternativeName | Ahn, Chul Woo | - |
dc.contributor.alternativeName | Lee, Hyun Chul | - |
dc.contributor.alternativeName | Yim, Yeong Shin | - |
dc.contributor.alternativeName | Cha, Bong Soo | - |
dc.contributor.affiliatedAuthor | Kang, Eun Seok | - |
dc.contributor.affiliatedAuthor | Kim, Yu Seun | - |
dc.contributor.affiliatedAuthor | Kim, Chul Hoon | - |
dc.contributor.affiliatedAuthor | Ahn, Chul Woo | - |
dc.contributor.affiliatedAuthor | Lee, Hyun Chul | - |
dc.contributor.affiliatedAuthor | Yim, Yeong Shin | - |
dc.contributor.affiliatedAuthor | Cha, Bong Soo | - |
dc.contributor.affiliatedAuthor | Kim, In Sook | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 11 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 191 | - |
dc.citation.endPage | 198 | - |
dc.identifier.bibliographicCitation | PHARMACOGENOMICS JOURNAL, Vol.11(3) : 191-198, 2011 | - |
dc.identifier.rimsid | 27966 | - |
dc.type.rims | ART | - |
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