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

Mary Corless, Aoife Kiely, Neville McClenaghan, Peter Flatt, Philip Newsholme

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.
LanguageEnglish
Pages719-727
JournalJournal of Endrocrinology
Volume190
Issue number3
DOIs
Publication statusPublished - Sep 2006

Fingerprint

Insulin-Secreting Cells
Glutamine
Signal Transduction
Transcription Factors
Gene Expression
Cell Line
Insulin
Glutamic Acid
Proteins
Genes
Calcineurin
N-Methylaspartate
Microarray Analysis
Oligonucleotide Array Sequence Analysis
N-Methyl-D-Aspartate Receptors
Down-Regulation
Amino Acids
Food

Cite this

@article{981e364665b34f56a6ae2ccefa276472,
title = "Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic beta-cell line",
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.",
author = "Mary Corless and Aoife Kiely and Neville McClenaghan and Peter Flatt and Philip Newsholme",
year = "2006",
month = "9",
doi = "10.1677/joe.1.06892",
language = "English",
volume = "190",
pages = "719--727",
journal = "Journal of Endrocrinology",
issn = "0022-0795",
number = "3",

}

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; Newsholme, Philip.

In: Journal of Endrocrinology, Vol. 190, No. 3, 09.2006, p. 719-727.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene, and protein expression in a clonal pancreatic beta-cell line

AU - Corless, Mary

AU - Kiely, Aoife

AU - McClenaghan, Neville

AU - Flatt, Peter

AU - Newsholme, Philip

PY - 2006/9

Y1 - 2006/9

N2 - 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.

AB - 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.

U2 - 10.1677/joe.1.06892

DO - 10.1677/joe.1.06892

M3 - Article

VL - 190

SP - 719

EP - 727

JO - Journal of Endrocrinology

T2 - Journal of Endrocrinology

JF - Journal of Endrocrinology

SN - 0022-0795

IS - 3

ER -