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首页> 外文期刊>Life sciences >Endotoxin induced hyperlactatemia and hypoglycemia is linked to decreased mitochondrial phosphoenolpyruvate carboxykinase
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Endotoxin induced hyperlactatemia and hypoglycemia is linked to decreased mitochondrial phosphoenolpyruvate carboxykinase

机译：内毒素诱导的超疾病和低血糖与下降的线粒体磷丙酮酸羧基酶相关联

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Aims: Phosphoenolpyruvate carboxykinase (PEPCK) is the rate limiting enzyme for gluconeogenesis, and plays a key role in recycling lactate for glucose production. It is synthesized as two separate isoforms; cytosolic (PEPCK-C, gene code; PCK1) and mitochondrial (PEPCK-M, gene code; PCK2). Previous studies of gluconeogenesis in endotoxemia have focused solely on PCK1. We investigated the relative roles of the two isoforms in hepatic and renal gluconeogenesis in a rat model of endotoxic shock, and in cultured hepatocytes. Main methods: Rats were administered lipopolysaccharide (6 mg/kg; LPS) for 6 h. Cultured cells were incubated with lactate (5 mM) with or without tumor necrosis factor alpha (1 - 10 ng/ml). Rat liver and kidney samples as well as cultured cells were subjected to subcellular fractionation to produce mitochondrial and cytosolic fractions for PEPCK activity assay. PCK1 and PCK2 mRNA levels were measured using quantitative RT-PCR.Key findings: In rat endotoxemia, hepatic PCK2 mRNA and PEPCK-M enzyme activity decreased by 53% and 38%, compared to sham controls. Hepatic PCK1 mRNA levels increased by 44%, but PEPCK-C enzyme activity remained unchanged. The changes in hepatic PEPCK-M coincided with a marked hypoglycemia and hyperlactatemia as well as elevated plasma interleukin 1 beta (IL1beta). incubation of cultured hepatocytes with TNF-alpha inhibited lactate-induced increases in glucose production, PCK2 mRNA levels and PEPCK-M enzyme activity but had no effect on PCK1 mRNA levels or PEPCK-C activity.Significance: These results indicate that decreases in hepatic PEPCK-M play a key role in the manifestation of hyperlactatemia and hypoglycemia in endotoxemia.
机译：目的：磷酸胆管胆管羧酮（Pepck）是葡糖生成的速率限制酶，在回收血糖生产中发挥关键作用。合成为两个单独的同种型;细胞溶溶胶（Pepck-C，基因号; PCK1）和线粒体（Pepck-M，基因编码; PCK2）。先前的内毒血症葡糖生成的研究仅集中在PCK1上。我们研究了两种同种型在内毒性休克大鼠模型中的两种同种型的相对统一性，培养的肝细胞。主要方法：将大鼠施用脂多糖（6mg / kg; LPS）6小时。将培养的细胞与乳酸（5mm）一起温育，或没有肿瘤坏死因子α（1-10ng / ml）。对大鼠肝脏和肾脏样品以及培养的细胞进行亚细胞分级，以产生PEPCK活性测定的线粒体和细胞溶质级分。使用定量RT-PCR，测量PCK1和PCK2 mRNA水平：与假对照相比，在大鼠内毒血症中，肝PCK2 mRNA和PEPCK-M酶活性降低53％和38％。肝PCK1 mRNA水平增加44％，但PEPCK-C酶活性保持不变。肝Pepck-M的变化与明显的低血糖和过甲虫血症以及升高的血浆白细胞介素1β（IL1Beta）。用TNF-α培养的肝细胞培养抑制乳酸致血糖产生，PCK2 mRNA水平和PEPCK-M酶活性的增加，但对PCK1 mRNA水平或PEPCK-C活性没有影响。重要性：这些结果表明肝PEPCK中减少-M在内毒素血症的超疾病和低血糖症的表现中发挥关键作用。

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