Overexpression of the malate-aspartate NADH shuttle member Aralar1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism.
Overexpression of the malate-aspartate NADH shuttle member Aralar1 in the clonal beta-cell line BRIN-BD11 enhances amino-acid-stimulated insulin secretion and cell metabolism.
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DOI：
10.1042/cs20090126
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发表时间：
2009-09-01
期刊：
影响因子：
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通讯作者：
Newsholme P
中科院分区：
文献类型：
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作者：
Bender K;Maechler P;McClenaghan NH;Flatt PR;Newsholme P
在本研究中，我们研究了重组腺病毒AdCA-Aralar1（天冬氨酸-谷氨酸载体1）对葡萄糖和氨基酸反应性克隆胰岛素分泌细胞株BRIN-BD11代谢、功能和分泌特性的影响。Aralar1过表达增加了长期（24 h）和急性（20 min）葡萄糖和氨基酸刺激的胰岛素分泌、细胞葡萄糖代谢、l -丙氨酸和l -谷氨酰胺消耗、细胞ATP和谷氨酸浓度，并刺激谷氨酸释放。然而，细胞甘油三酯和糖原含量下降，乳酸产量下降。这些发现表明，增加的苹果酸-天冬氨酸穿梭活性积极改变β细胞代谢，从而增加糖酵解能力，刺激-分泌偶联，最终增强胰岛素分泌。我们认为Aralar1是胰岛素分泌细胞中一个关键的代谢控制位点。
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 β-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.