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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

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

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 11:10

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