Overexpression of the malate-aspartate NADH shuttle member Aralar1 in the clonal ß-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism
MetadataShow full item record
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. Aralar1 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 ß-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.
Showing items related by title, author, creator and subject.
Toll-like receptor agonist induced changes in clonal rat BRIN-BD11 ß-cell insulin secretion and signal transductionKiely, A.; Robinson, A.; McClenaghan, N.; Flatt, P.; Newsholme, Philip (2009)Evidence for involvement of toll-like receptors (TLRs) (e.g. TLR4 and TLR2, whose agonists include lipopolysaccharides (LPS) and saturated fatty acids) in altered patterns of signalling in adipose, liver and muscle from ...
Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic ß-cell line and mouse isletsDa Silva Krause, M.; Bittencourt, A.; de Bittencourt, P.; McClenaghan, N.; Flatt, P.; Murphy, C.; Newsholme, Philip (2012)Interleukin-6 (IL6) has recently been reported to promote insulin secretion in a glucagon-like peptide-1-dependent manner. Herein, the direct effects of IL6 (at various concentrations from 0 to 1000 pg/ml) on pancreatic ...
Newsholme, Philip; Cruzat, Vinicius; Arfuso, Frank; Keane, Kevin (2014)Pancreatic ß-cell function is of critical importance in the regulation of fuel homoeostasis, and metabolic dysregulation is a hallmark of diabetes mellitus (DM). The ß-cell is an intricately designed cell type that couples ...