Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin

James Brown, Alex C. Conner, Janet E. Digby, Kenya L. Ward, Manjunath Ramanjaneya, Harpal S. Randeva, Simon J. Dunmore

Research output: Contribution to journalArticlepeer-review


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 beta-cell. 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.
Original languageEnglish
Pages (from-to)944-949
Number of pages6
Issue number5
Early online date13 Feb 2010
Publication statusPublished - May 2010


  • adiponectin
  • animals
  • cell line
  • cell survival
  • enzyme-linked immunosorbent assay
  • nonesterified fatty acids
  • insulin-secreting cells
  • leptin
  • mitogen-activated protein kinase 1
  • mitogen-activated protein kinase 3
  • peroxisome proliferator-activated receptors
  • rats
  • adiponectin receptors
  • peptide
  • beta-cell
  • cell viability
  • LPL
  • PDX-1


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