11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HCl stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old maleSprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus.

中文翻译：

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肝 11 β-羟基类固醇脱氢酶 1 参与大鼠酸中毒应激产生的葡萄糖代谢改变。

11 种 β-羟基类固醇脱氢酶 (HSD) 酶可调节靶器官中糖皮质激素的活性。HSD1 是现有的两种同种型之一，主要位于中枢神经系统、肝脏和脂肪组织中。HSD1 参与肥胖、胰岛素抵抗、动脉高血压和代谢综合征等疾病的发病机制。HCl 超负荷产生的压力会引发代谢性酸中毒并增加肝脏 HSD1 活性，这与磷酸烯醇丙酮酸羧激酶（一种由糖皮质激素激活的糖异生调节酶）增加相关，从而增加血糖和糖原分解。本研究的目的是分析 HCl 应激引发的代谢改变是否是由于肝脏 HSD1 活性增加所致。甘草次酸，一种有效的 HDS 抑制剂，Sprague Dawley大鼠研究肝脏 HSD1、磷酸烯醇式丙酮酸羧激酶 (PECPK) 和糖原磷酸化酶活性和血浆葡萄糖水平的变化。据观察，所有这些参数在应激动物中都增加了，但用甘草次酸处理显着降低了它们的水平。总之，我们的结果表明 HSD1 参与应激诱导的碳水化合物紊乱，并且可能有助于 HSD1 抑制剂对碳水化合物代谢的影响及其在代谢综合征和非胰岛素依赖型糖尿病研究中的相关性。