Leptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells.
dc.contributor.author | Brown, James E. P. | |
dc.contributor.author | Dunmore, Simon J. | |
dc.date.accessioned | 2008-03-12T10:03:16Z | |
dc.date.available | 2008-03-12T10:03:16Z | |
dc.date.issued | 2007 | |
dc.identifier.citation | Diabetes/Metabolism Research Reviews, 23(6): 497-502 | |
dc.identifier.issn | 1520-7552 | |
dc.identifier.pmid | 17318810 | |
dc.identifier.doi | 10.1002/dmrr.726 | |
dc.identifier.uri | http://hdl.handle.net/2436/20393 | |
dc.description.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. | |
dc.language.iso | en | |
dc.publisher | Wiley Interscience | |
dc.relation.url | http://www3.interscience.wiley.com/cgi-bin/abstract/114123262/ | |
dc.subject | Leptin | |
dc.subject | Apoptosis | |
dc.subject | Beta-cell | |
dc.subject | BCL-2 | |
dc.subject | Bax | |
dc.subject.mesh | Animals | |
dc.subject.mesh | Apoptosis | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Culture Media, Serum-Free | |
dc.subject.mesh | Insulin-Secreting Cells | |
dc.subject.mesh | Leptin | |
dc.subject.mesh | Proto-Oncogene Proteins c-bcl-2 | |
dc.subject.mesh | RNA, Messenger | |
dc.subject.mesh | Rats | |
dc.subject.mesh | bcl-2-Associated X Protein | |
dc.title | Leptin decreases apoptosis and alters BCL-2 : Bax ratio in clonal rodent pancreatic beta-cells. | |
dc.type | Journal article | |
html.description.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. |