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

Research output: Contribution to journalArticle

View graph of relations Save citation

Authors

Research units

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.

Request a copy

Request a copy

Details

Original languageEnglish
Pages (from-to)944-949
Number of pages6
JournalPeptides
Volume31
Issue number5
Early online date13 Feb 2010
DOIs
Publication statusPublished - 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

Employable Graduates; Exploitable Research

Copy the text from this field...