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

• Published in: Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2010-05, Vol.31 (5), p.944-949
• Main Authors: Brown, James E.P., Conner, Alex C., Digby, Janet E., Ward, Kenya L., Ramanjaneya, Manjunath, Randeva, Harpal S., Dunmore, Simon J.
• Format: Article
• Language: English
• Subjects: Activation; Adiponectin; Adiponectin - agonists; Adiponectin - metabolism; Animals; Attenuation; Beta-cell; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Cell viability; Control; Enzyme-Linked Immunosorbent Assay; Fatty acids; Fatty Acids, Nonesterified - pharmacology; Fundamental and applied biological sciences. Psychology; Gene expression; Insulin; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - drug effects; Leptin; Leptin - pharmacology; LPL; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; PDX-1; Peptide; Peroxisome Proliferator-Activated Receptors - agonists; Rats; Receptors; Receptors, Adiponectin - metabolism; Vertebrates: endocrinology; Viability
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2010.02.004

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.