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Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor-1 mediated inhibition of pancreatic beta cell death.

DC FieldValueLanguage
dc.contributor.author이은직-
dc.date.accessioned2016-05-16T11:23:53Z-
dc.date.available2016-05-16T11:23:53Z-
dc.date.issued2002-
dc.identifier.issn0013-7227-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/144461-
dc.description.abstractTo 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.statementOfResponsibilityopen-
dc.format.extent3802~3812-
dc.relation.isPartOfENDOCRINOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCell Death/drug effects-
dc.subject.MESHCell Death/physiology-
dc.subject.MESHCell Line-
dc.subject.MESHChromones/pharmacology-
dc.subject.MESHCulture Media, Serum-Free-
dc.subject.MESHCyclic AMP Response Element-Binding Protein/drug effects-
dc.subject.MESHCyclic AMP Response Element-Binding Protein/physiology-
dc.subject.MESHEnzyme Activation/physiology-
dc.subject.MESHEnzyme Inhibitors/pharmacology-
dc.subject.MESHFlavonoids/pharmacology-
dc.subject.MESHInsulin-Like Growth Factor I/pharmacology-
dc.subject.MESHInsulin-Like Growth Factor I/physiology*-
dc.subject.MESHIslets of Langerhans/drug effects-
dc.subject.MESHIslets of Langerhans/physiology*-
dc.subject.MESHMitogen-Activated Protein Kinases/metabolism-
dc.subject.MESHMorpholines/pharmacology-
dc.subject.MESHPhosphatidylinositol 3-Kinases/metabolism*-
dc.subject.MESHPhosphorylation/drug effects-
dc.subject.MESHProtein-Serine-Threonine Kinases*-
dc.subject.MESHProto-Oncogene Proteins/metabolism-
dc.subject.MESHProto-Oncogene Proteins c-akt-
dc.subject.MESHRats-
dc.titleActivation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor-1 mediated inhibition of pancreatic beta cell death.-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorWenli Liu-
dc.contributor.googleauthorCatherine Chin Chance-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorWilliam L. Lowe Jr-
dc.identifier.doi10.1210/en.2002-220058-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03050-
dc.relation.journalcodeJ00772-
dc.identifier.eissn1945-7170-
dc.identifier.pmid12239091-
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2002-220058-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.rights.accessRightsnot free-
dc.citation.volume143-
dc.citation.number10-
dc.citation.startPage3802-
dc.citation.endPage3812-
dc.identifier.bibliographicCitationENDOCRINOLOGY, Vol.143(10) : 3802-3812, 2002-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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