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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0160v1 202/3/365    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kiely, A. Articles by Newsholme, P. Search for Related Content PubMed PubMed Citation Articles by Kiely, A. Articles by Newsholme, P.

A Kiely, Biomolecular & Biomedical Science, UCD Dublin, Dublin, Ireland
A Robinson, Conway Institute, UCD Dublin, Dublin, Ireland
N McClenaghan, School of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom
P Flatt, School of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom
P Newsholme, Biomolecular & Biomedical Science, UCD Dublin, Dublin, Dublin 4, Ireland

Correspondence: Philip Newsholme, Email: philip.newsholme{at}ucd.ie

Evidence for involvement of Toll like receptors (e.g. TLR4 and TLR2, whose agonists include lipopolysaccharides and saturated fatty acids) in altered patterns of signalling in adipose, liver and muscle from animal models of insulin resistance and obesity has been published. We have now extended this area of research and have determined the effects of LPS on cell viability, insulin secretion, insulin signalling and metabolism in a clonal β-cell line. BRIN BD11 β-cells were treated for 24 hours with increasing concentrations of LPS. Chronic (24 h) and acute (20 min) insulin secretion, insulin content and parameters of cell metabolism and insulin signalling were determined. Incubation of BRIN-BD11 cells for 24 hours in the presence of increasing concentrations of the TLR4 ligand LPS significantly decreased chronic (24 hour) insulin secretion from 1.09 ± 0.19 to 0.76 ± 0.18 µg insulin / mg protein in the presence of 100 ng/ml LPS (p < 0.05). There was no change in acute (20 min) stimulated insulin secretion, or insulin content. Cell metabolism was not changed. IRβ expression levels were increased significantly from 1 ± 0.52 to 8.6 ± 1.83 units (p < 0.01), whereas calcineurin activity and Akt phosphorylation were significantly (p<0.01 and p<0.05 respectively) reduced in response to 24hr incubation in the presence of LPS. There was no change in IRS-1 protein expression or phosphorylation after 24 hours. Further incubation for 24 hours in the absence of LPS resulted in a recovery of chronic insulin secretion. The negative beta cell effects of LPS may contribute to hyperglycaemia in vivo.