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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

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

Bender, Katrin, Maechler, Pierre, McClenaghan, Neville H., Flatt, Peter and Newsholme, Philip (2009) 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. CLINICAL SCIENCE, 117 (9-10). pp. 321-330. [Journal article]

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DOI: 10.1042/CS20090126

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.

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:2883
Deposited By:Professor Peter Flatt
Deposited On:15 Dec 2009 16:10
Last Modified:15 Jun 2011 11:10

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