2.50
Hdl Handle:
http://hdl.handle.net/2436/20393
Title:
Leptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells.
Authors:
Brown, James E. P.; Dunmore, Simon J.
Abstract:
AIMS/HYPOTHESIS: The adipocyte derived peptide hormone leptin is known to regulate apoptosis and cell viability in several cells and tissues, as well as having several pancreatic islet beta-cell specific effects such as inhibition of glucose-stimulated insulin secretion. This study investigated the effects of leptin upon apoptosis induced by serum depletion and on expression of the apoptotic regulators B-cell leukaemia 2 gene product (BCL-2) and BCL2-associated X protein (Bax) in the glucose-responsive BRIN-BD11 beta-cell line. METHODS: BRIN-BD11 cells were cultured in RPMI 1640 and subsequently serum depleted +/- leptin (10 and 50 ng/mL) for 24 h. Cell viability and apoptosis were measured using a modified MTS assay and TUNEL/YO-PRO-1 assays, respectively. BCL-2 and Bax expression were measured by real-time PCR and Western blotting. RESULTS: Leptin caused a reduction in serum-depleted apoptosis, although it failed to have any effect on the overall cell viability, causing a 68% shift from apoptosis to necrosis. Leptin significantly increased the level of BCL-2 mRNA expression (150% compared to serum depletion alone), without altering Bax mRNA expression. At the protein level, leptin increased BCL-2 and decreased Bax, altering the BCL-2 : Bax ratio. CONCLUSIONS: We conclude that leptin reduces apoptosis in beta-cells at physiological concentrations, possibly via its ability to up-regulate BCL-2 and Bax expression.
Citation:
Diabetes/Metabolism Research Reviews, 23(6): 497-502
Publisher:
Wiley Interscience
Issue Date:
2007
URI:
http://hdl.handle.net/2436/20393
DOI:
10.1002/dmrr.726
PubMed ID:
17318810
Additional Links:
http://www3.interscience.wiley.com/cgi-bin/abstract/114123262/
Type:
Article
Language:
en
ISSN:
1520-7552
Appears in Collections:
Diabetes, Physiology and Molecular Medicine Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBrown, James E. P.-
dc.contributor.authorDunmore, Simon J.-
dc.date.accessioned2008-03-12T10:03:16Z-
dc.date.available2008-03-12T10:03:16Z-
dc.date.issued2007-
dc.identifier.citationDiabetes/Metabolism Research Reviews, 23(6): 497-502en
dc.identifier.issn1520-7552-
dc.identifier.pmid17318810-
dc.identifier.doi10.1002/dmrr.726-
dc.identifier.urihttp://hdl.handle.net/2436/20393-
dc.description.abstractAIMS/HYPOTHESIS: The adipocyte derived peptide hormone leptin is known to regulate apoptosis and cell viability in several cells and tissues, as well as having several pancreatic islet beta-cell specific effects such as inhibition of glucose-stimulated insulin secretion. This study investigated the effects of leptin upon apoptosis induced by serum depletion and on expression of the apoptotic regulators B-cell leukaemia 2 gene product (BCL-2) and BCL2-associated X protein (Bax) in the glucose-responsive BRIN-BD11 beta-cell line. METHODS: BRIN-BD11 cells were cultured in RPMI 1640 and subsequently serum depleted +/- leptin (10 and 50 ng/mL) for 24 h. Cell viability and apoptosis were measured using a modified MTS assay and TUNEL/YO-PRO-1 assays, respectively. BCL-2 and Bax expression were measured by real-time PCR and Western blotting. RESULTS: Leptin caused a reduction in serum-depleted apoptosis, although it failed to have any effect on the overall cell viability, causing a 68% shift from apoptosis to necrosis. Leptin significantly increased the level of BCL-2 mRNA expression (150% compared to serum depletion alone), without altering Bax mRNA expression. At the protein level, leptin increased BCL-2 and decreased Bax, altering the BCL-2 : Bax ratio. CONCLUSIONS: We conclude that leptin reduces apoptosis in beta-cells at physiological concentrations, possibly via its ability to up-regulate BCL-2 and Bax expression.en
dc.language.isoenen
dc.publisherWiley Interscienceen
dc.relation.urlhttp://www3.interscience.wiley.com/cgi-bin/abstract/114123262/en
dc.subjectLeptinen
dc.subjectApoptosisen
dc.subjectBeta-cellen
dc.subjectBCL-2en
dc.subjectBaxen
dc.subject.meshAnimalsen
dc.subject.meshApoptosisen
dc.subject.meshCell Lineen
dc.subject.meshCulture Media, Serum-Freeen
dc.subject.meshInsulin-Secreting Cellsen
dc.subject.meshLeptinen
dc.subject.meshProto-Oncogene Proteins c-bcl-2en
dc.subject.meshRNA, Messengeren
dc.subject.meshRatsen
dc.subject.meshbcl-2-Associated X Proteinen
dc.titleLeptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells.en
dc.typeArticleen
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