Role of hepatic AMPK activation in glucose metabolism and dexamethasone-induced regulation of AMPK expression
Role of hepatic AMPK activation in glucose metabolism and dexamethasone-induced regulation of AMPK expression
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DOI：
10.1016/j.diabres.2005.12.011
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发表时间：
2006-08-01
影响因子：
5.1
通讯作者：
Asano, Tomoichiro
中科院分区：
文献类型：
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作者：
Viana, Amelia Y. I.;Sakoda, Hideyuki;Asano, Tomoichiro
为了阐明AMPK在肝葡萄糖代谢中的作用，通过腺病毒介导的基因转移过表达AMPK α 1亚基的显性阴性（DN）、组成型活性（CA）形式和对照载体LacZ。病毒注射后5天，CA小鼠肝脏AMPK活性是DN小鼠的5倍。DN小鼠明显葡萄糖不耐受，空腹血糖水平较高（DN 82.3 +/- 0.7 mg/dl，CA 42.5 +/- 4.8 mg/dl和LacZ 54.3 +/- 2.4 mg/dl）。糖尿病肾病小鼠肾脏中促血管生成关键酶PEPCK的mRNA表达分别比CA和LacZ高131.54%和48.92%。因此，肝脏AMPK激活在抑制新生血管形成中起作用，这可能是导致CA小鼠空腹血糖水平降低的原因。我们还研究了地塞米松对大鼠肝脏、小鼠肝脏以及原代培养的肝细胞中肝脏AMPK表达和活性的影响。皮下注射地塞米松（1 mg/d）5天可显著上调肝脏AMPK α 1和α 2表达。同样地，用地塞米松（1 μ M）处理原代培养的大鼠肝细胞增加了AMPK α 1亚基的表达，AICAR诱导的AMPK磷酸化和激酶活性。尽管AMPK表达的增加不能归因于地塞米松诱导的葡萄糖耐受不良，但综合我们的结果，我们提出了AMPK控制肝脏葡萄糖输出及其表达的可能性，肝脏可能受到各种激素和生长因子的调节。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
To elucidate the role of AMPK in hepatic glucose metabolism, dominant negative (DN), constitutively active (CA) forms of the AMPK alpha 1 subunit and control vector LacZ were overexpressed by means of adenovirus-mediated gene transfer. Five days after virus injection, hepatic AMPK activity was five-fold higher in CA mice than in DN mice. DN mice were apparently glucose intolerant with a higher fasting plasma glucose level (DN 82.3 +/- 0.7 mg/dl, CA 42.5 +/- 4.8 mg/dl and LacZ 54.3 +/- 2.4 mg/dl). PEPCK, a gluconeogenic key enzyme, mRNA was increased 131.54% and 48.92% in DN mice compared to that of CA and LacZ, respectively. Thus, hepatic AMPK activation plays a role in the suppression of gluconeogenesis and this might be the cause of decreased fasting plasma glucose level in CA mice.We also investigated the effects of dexamethasone on hepatic AMPK expression and activity in rat liver, mice liver, as well as primary cultured hepatocytes. Subcutaneously injecting mice with dexamethasone (1 mg/day) for 5 days significantly upregulated hepatic AMPK alpha 1 and alpha 2 expressions. Similarly, the treatment of primary cultured rat hepatocytes with dexamethasone (I mu M) increased expression of the AMPK alpha 1 subunit, AICAR-induced AMPK phosphorylation and kinase activity.Although increased AMPK expression cannot be attributed to dexamethasone-induced glucose intolerance, taken together our results raise the possibility that AMPK control liver glucose output and its expression in, liver might be modulated by various hormones and growth factors. (c) 2006 Elsevier Ireland Ltd. All rights reserved.