Regulation of beta-cell viability and gene expression by distinct agonist fragments of adiponectin
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Authors
Brown, James E. P.Conner, Alex C..
Digby, Janet E.
Ward, Kenya L.
Ramanjaneya, Manjunath
Randeva, Harpal S.
Dunmore, Simon J.
Issue Date
2010
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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.Citation
Peptides, 31(5): 944-949Journal
PeptidesAdditional Links
http://linkinghub.elsevier.com/retrieve/pii/S0196978110000586Type
Journal articleLanguage
enISSN
01969781ae974a485f413a2113503eed53cd6c53
10.1016/j.peptides.2010.02.004