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Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor-1 mediated inhibition of pancreatic beta cell death.
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이은직 | - |
dc.date.accessioned | 2016-05-16T11:23:53Z | - |
dc.date.available | 2016-05-16T11:23:53Z | - |
dc.date.issued | 2002 | - |
dc.identifier.issn | 0013-7227 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/144461 | - |
dc.description.abstract | To begin to determine whether IGF-I treatment represents a potential means of enhancing the survival of islet cell grafts after transplantation, the present studies established a model of β-cell death secondary to loss of trophic support and examined the ability of IGF-I to prevent cell death. The studies were performed using the rat pancreatic β-cell line, INS-1. Incubating INS-1 cells in RPMI 1640 and 0.25% BSA for 48 h increased cell death, as determined by lactate dehydrogenase release, compared with that of cells maintained in RPMI and 10% fetal calf serum. Addition of 100 ng/ml IGF-I to the serum-free medium decreased lactate dehydrogenase release to a level comparable to that found in cells maintained in fetal calf serum. Similar results were seen using a mouse β-cell line, MIN6, infected with an adenovirus expressing IGF-I. Examination of IGF-I-stimulated signaling demonstrated that IGF-I increased the phosphorylation of protein kinase B in both cell lines, whereas IGF-I-induced phosphorylation of the MAPKs, ERK1 and -2, was observed only in INS-1 cells. The effect of IGF-I on phosphorylation of substrates of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B was also examined in INS-1 cells. IGF-I increased the phosphorylation of glycogen synthase kinase 3β, BAD, FKHR, and p70S6 kinase. Another pathway that has been shown to mediate the protective of IGF-I in some cell types is activation of cAMP response element-binding protein (CREB). IGF-I increased CREB phosphorylation at a concentration as low as 10 ng/ml, and this effect was inhibited by H89, a PKA inhibitor, and PD98059, a MAPK kinase inhibitor. Consistent with the effect of IGF-I on CREB phosphorylation, IGF-I increased the transcriptional activity of CREB, although it had no effect on CREB binding to DNA. Use of inhibitors of the PI 3-kinase (LY 294002) or ERK (PD98059) pathways or CREB phosphorylation (H89) in the cell death assay demonstrated partial abrogation of the protective effect of IGF-I with LY 294002. These data demonstrate that IGF-I protects pancreatic β-cells from cell death secondary to loss of trophic support and that, although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in β-cells. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 3802~3812 | - |
dc.relation.isPartOf | ENDOCRINOLOGY | - |
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 | Animals | - |
dc.subject.MESH | Cell Death/drug effects | - |
dc.subject.MESH | Cell Death/physiology | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Chromones/pharmacology | - |
dc.subject.MESH | Culture Media, Serum-Free | - |
dc.subject.MESH | Cyclic AMP Response Element-Binding Protein/drug effects | - |
dc.subject.MESH | Cyclic AMP Response Element-Binding Protein/physiology | - |
dc.subject.MESH | Enzyme Activation/physiology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology | - |
dc.subject.MESH | Flavonoids/pharmacology | - |
dc.subject.MESH | Insulin-Like Growth Factor I/pharmacology | - |
dc.subject.MESH | Insulin-Like Growth Factor I/physiology* | - |
dc.subject.MESH | Islets of Langerhans/drug effects | - |
dc.subject.MESH | Islets of Langerhans/physiology* | - |
dc.subject.MESH | Mitogen-Activated Protein Kinases/metabolism | - |
dc.subject.MESH | Morpholines/pharmacology | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/metabolism* | - |
dc.subject.MESH | Phosphorylation/drug effects | - |
dc.subject.MESH | Protein-Serine-Threonine Kinases* | - |
dc.subject.MESH | Proto-Oncogene Proteins/metabolism | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt | - |
dc.subject.MESH | Rats | - |
dc.title | Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor-1 mediated inhibition of pancreatic beta cell death. | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Wenli Liu | - |
dc.contributor.googleauthor | Catherine Chin Chance | - |
dc.contributor.googleauthor | Eun Jig Lee | - |
dc.contributor.googleauthor | William L. Lowe Jr | - |
dc.identifier.doi | 10.1210/en.2002-220058 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A03050 | - |
dc.relation.journalcode | J00772 | - |
dc.identifier.eissn | 1945-7170 | - |
dc.identifier.pmid | 12239091 | - |
dc.identifier.url | http://press.endocrine.org/doi/abs/10.1210/en.2002-220058 | - |
dc.contributor.alternativeName | Lee, Eun Jig | - |
dc.contributor.affiliatedAuthor | Lee, Eun Jig | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 143 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 3802 | - |
dc.citation.endPage | 3812 | - |
dc.identifier.bibliographicCitation | ENDOCRINOLOGY, Vol.143(10) : 3802-3812, 2002 | - |
dc.identifier.rimsid | 49729 | - |
dc.type.rims | ART | - |
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