Journal of Endocrinology (2006) 190, 719-727 DOI: 10.1677/joe.1.06892
© 2006 Society for Endocrinology
Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic ß-cell line
Mary Corless,
Aoife Kiely,
Neville H McClenaghan1,
Peter R Flatt1 and
Philip Newsholme
School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
1 School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK
(Requests for offprints should be addressed to P Newsholme; Email: philip.newsholme{at}ucd.ie)
Supplementary material
Supplementary data table 1 associated with this article can be found in the online version of Journal of Endocrinology at http://joe.endocrinology-journals.org/content/vol190/issue3.
We have investigated the effects of prolonged exposure (24 h) to the amino acid L-glutamine, on gene and protein expression using clonal BRIN-BD11 ß-cells. Expression profiling of BRIN-BD11 cells was performed using oligonucleotide microarray analysis. Culture for 24 h with 10 mM L-glutamine compared with 1 mM resulted in substantial changes in gene expression with 148 genes upregulated more than 1.8-fold, and 18 downregulated more than 1.8-fold, including many genes involved in cellular signaling, metabolism, gene regulation, and the insulin-secretory response. Subsequent functional experiments confirmed that L-glutamine increased the activity of the Ca2+ regulated phosphatase calcineurin and the transcription factor Pdx1. Additionally, we demonstrated that ß-cell-derived L-glutamate was released into the extracellular medium at high rates. As calcineurin is a regulator of the glutamate N-methyl-D-aspartate (NMDA) receptor activity, we investigated the action of NMDA on nutrient-induced insulin secretion, and demonstrated suppressed insulin release. These observations indicate important long-term effects of L-glutamine in regulating ß-cell gene expression, signaling, and secretory function.
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Copyright © 2006 by the Society for Endocrinology.