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 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 language | English |
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Pages (from-to) | 944-949 |
Number of pages | 6 |
Journal | Peptides |
Volume | 31 |
Issue number | 5 |
Early online date | 13 Feb 2010 |
DOIs | |
Publication status | Published - May 2010 |
Keywords
- 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