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Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic beta-cell line

Corless, Mary, Kiely, Aoife, McClenaghan, Neville, Flatt, Peter and Newsholme, Philip (2006) Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic beta-cell line. JOURNAL OF ENDOCRINOLOGY, 190 (3). pp. 719-727. [Journal article]

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DOI: 10.1677/joe.1.06892

Abstract

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 beta-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 beta-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 beta-cell gene expression, signaling, and secretory function.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2966
Deposited By: Professor Peter Flatt
Deposited On:17 Dec 2009 15:08
Last Modified:15 Jun 2011 10:10

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