Overexpression of the malate-aspartate NADH shuttle member Aralar 1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism

Katrin Bender, Pierre Maechler, Neville H. McClenaghan, Peter Flatt, Philip Newsholme

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

In the present study, we have investigated the effects of the transduction with recombinant adenovirus AdCA-Aralar1 (aspartate-glutamate carrier 1) on the metabolism, function and secretory properties of the glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar I overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L-alanine and L-glutamine consumption, cellular ATP and glutamate concentrations, and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These findings indicate that increased malate-aspartate shuttle activity positively shifted beta-cell metabolism, thereby increasing glycolysis capacity, stimulus-secretion coupling and, ultimately, enhancing insulin secretion. We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells.
LanguageEnglish
Pages321-330
JournalClinical Science
Volume117
Issue number9-10
DOIs
Publication statusPublished - Nov 2009

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Aspartic Acid
NAD
Insulin-Secreting Cells
Insulin
Amino Acids
Glucose
Cell Line
Glutamic Acid
Glycolysis
Glutamine
Glycogen
Adenoviridae
Alanine
Lactic Acid
Triglycerides
Adenosine Triphosphate
malic acid

Cite this

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title = "Overexpression of the malate-aspartate NADH shuttle member Aralar 1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism",
abstract = "In the present study, we have investigated the effects of the transduction with recombinant adenovirus AdCA-Aralar1 (aspartate-glutamate carrier 1) on the metabolism, function and secretory properties of the glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar I overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L-alanine and L-glutamine consumption, cellular ATP and glutamate concentrations, and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These findings indicate that increased malate-aspartate shuttle activity positively shifted beta-cell metabolism, thereby increasing glycolysis capacity, stimulus-secretion coupling and, ultimately, enhancing insulin secretion. We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells.",
author = "Katrin Bender and Pierre Maechler and McClenaghan, {Neville H.} and Peter Flatt and Philip Newsholme",
year = "2009",
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Overexpression of the malate-aspartate NADH shuttle member Aralar 1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism. / Bender, Katrin; Maechler, Pierre; McClenaghan, Neville H.; Flatt, Peter; Newsholme, Philip.

In: Clinical Science, Vol. 117, No. 9-10, 11.2009, p. 321-330.

Research output: Contribution to journalArticle

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AU - Flatt, Peter

AU - Newsholme, Philip

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AB - In the present study, we have investigated the effects of the transduction with recombinant adenovirus AdCA-Aralar1 (aspartate-glutamate carrier 1) on the metabolism, function and secretory properties of the glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar I overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L-alanine and L-glutamine consumption, cellular ATP and glutamate concentrations, and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These findings indicate that increased malate-aspartate shuttle activity positively shifted beta-cell metabolism, thereby increasing glycolysis capacity, stimulus-secretion coupling and, ultimately, enhancing insulin secretion. We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells.

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