Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin
dc.contributor.author | Brown, James E. P. | |
dc.contributor.author | Conner, Alex C.. | |
dc.contributor.author | Digby, Janet E. | |
dc.contributor.author | Ward, Kenya L. | |
dc.contributor.author | Ramanjaneya, Manjunath | |
dc.contributor.author | Randeva, Harpal S. | |
dc.contributor.author | Dunmore, Simon J. | |
dc.date.accessioned | 2010-10-26T14:35:15Z | |
dc.date.available | 2010-10-26T14:35:15Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Peptides, 31(5): 944-949 | |
dc.identifier.issn | 01969781 | |
dc.identifier.doi | 10.1016/j.peptides.2010.02.004 | |
dc.identifier.uri | http://hdl.handle.net/2436/113833 | |
dc.description.abstract | Obesity is an established risk factor for type 2 diabetes. Activation of the adiponectin receptors has a clear role in improving insulin resistance although conflicting evidence exists for its effects on pancreatic beta-cells. Previous reports have identified both adiponectin receptors (ADR-1 and ADR-2) in the betacell. Recent evidence has suggested that two distinct regions of the adiponectin molecule, the globular domain and a small N-terminal region, have agonist properties. This study investigates the effects of two agonist regions of adiponectin on insulin secretion, gene expression, cell viability and cell signalling in the rat beta-cell line BRIN-BD11, as well as investigating the expression levels of adiponectin receptors (ADRs) in these cells. Cells were treated with globular adiponectin and adiponectin (15-36)±leptin to investigate cell viability, expression of key beta-cell genes and ERK1/2 activation. Both globular adiponectin and adiponectin (15-36) caused significant ERK1/2 dependent increases in cell viability. Leptin co-incubation attenuated adiponectin (15-36) but not globular adiponectin induced cell viability. Globular adiponectin, but not adiponectin (15-36), caused a significant 450% increase in PDX-1 expression and a 45% decrease in LPL expression. ADR-1 was expressed at a higher level than ADR-2, and ADR mRNA levels were differentially regulated by non-esterified fatty acids and peroxisome-proliferator-activated receptor agonists. These data provide evidence of roles for two distinct adiponectin agonist domains in the beta-cell and confirm the potentially important role of adiponectin receptor agonism in maintaining beta-cell mass. | |
dc.language.iso | en | |
dc.relation.url | http://linkinghub.elsevier.com/retrieve/pii/S0196978110000586 | |
dc.subject | Adiponectin | |
dc.subject | Peptide | |
dc.subject | Beta-cell | |
dc.subject | Leptin | |
dc.subject | Cell viability | |
dc.subject | LPL | |
dc.subject | PDX-1 | |
dc.title | Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin | |
dc.type | Journal article | |
dc.identifier.journal | Peptides | |
html.description.abstract | Obesity is an established risk factor for type 2 diabetes. Activation of the adiponectin receptors has a clear role in improving insulin resistance although conflicting evidence exists for its effects on pancreatic beta-cells. Previous reports have identified both adiponectin receptors (ADR-1 and ADR-2) in the betacell. Recent evidence has suggested that two distinct regions of the adiponectin molecule, the globular domain and a small N-terminal region, have agonist properties. This study investigates the effects of two agonist regions of adiponectin on insulin secretion, gene expression, cell viability and cell signalling in the rat beta-cell line BRIN-BD11, as well as investigating the expression levels of adiponectin receptors (ADRs) in these cells. Cells were treated with globular adiponectin and adiponectin (15-36)±leptin to investigate cell viability, expression of key beta-cell genes and ERK1/2 activation. Both globular adiponectin and adiponectin (15-36) caused significant ERK1/2 dependent increases in cell viability. Leptin co-incubation attenuated adiponectin (15-36) but not globular adiponectin induced cell viability. Globular adiponectin, but not adiponectin (15-36), caused a significant 450% increase in PDX-1 expression and a 45% decrease in LPL expression. ADR-1 was expressed at a higher level than ADR-2, and ADR mRNA levels were differentially regulated by non-esterified fatty acids and peroxisome-proliferator-activated receptor agonists. These data provide evidence of roles for two distinct adiponectin agonist domains in the beta-cell and confirm the potentially important role of adiponectin receptor agonism in maintaining beta-cell mass. |