Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation.
Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation.
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作者：
Quenneville S;Labouèbe G;Basco D;Metref S;Viollet B;Foretz M;Thorens B
下丘脑腹内侧核（VMN）参与低血糖的反调节反应。由低血糖激活的VMN神经元（葡萄糖抑制[GI]神经元）已被认为在这种反应中起关键作用，尽管尚未经过测试。在这里，我们发现，在VMN的Sf 1神经元中，AMPK显性负性形式的表达或AMPK α1和α2亚基基因的失活选择性地抑制GI神经元的活动。我们发现，Txn2，编码线粒体氧化还原酶，强烈下调AMPK活性的情况下，Sf1神经元中Txn2的重新表达恢复GI神经元的活动。在细胞系中，需要Txn2来限制葡萄糖减少诱导的活性氧产生。在生理学研究中，VMN中AMPK抑制后GI神经元活动的缺失对低血糖或进食的反调节激素反应没有影响。因此，AMPK是通过控制抗氧化酶Txn2的表达来控制GI神经元活性所必需的。然而，VMN GI神经元的葡萄糖感知能力对于低血糖的正常反调节反应是不需要的。相反，它可以表示在连接到VMN的位于外围的葡萄糖检测系统的低血糖感测受损的情况下的故障安全系统。
The ventromedial nucleus of the hypothalamus (VMN) is involved in the counterregulatory response to hypoglycemia. VMN neurons activated by hypoglycemia (glucose-inhibited [GI] neurons) have been assumed to play a critical although untested role in this response. Here, we show that expression of a dominant negative form of AMPK or inactivation of AMPK α1 and α2 subunit genes in Sf1 neurons of the VMN selectively suppressed GI neuron activity. We found that Txn2, encoding a mitochondrial redox enzyme, was strongly downregulated in the absence of AMPK activity and that reexpression of Txn2 in Sf1 neurons restored GI neuron activity. In cell lines, Txn2 was required to limit glucopenia-induced reactive oxygen species production. In physiological studies, absence of GI neuron activity after AMPK suppression in the VMN had no impact on the counterregulatory hormone response to hypoglycemia or on feeding. Thus, AMPK is required for GI neuron activity by controlling the expression of the antioxidant enzyme Txn2. However, the glucose-sensing capacity of VMN GI neurons is not required for the normal counterregulatory response to hypoglycemia. Instead, it may represent a fail-safe system in case of impaired hypoglycemia sensing by peripherally located glucose detection systems that are connected to the VMN.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
突触后AMPK→P21激活的激酶途径驱动禁食诱导的AGRP神经元中的突触可塑性。
影响因子：
16.2
作者：
Kong D;Dagon Y;Campbell JN;Guo Y;Yang Z;Yi X;Aryal P;Wellenstein K;Kahn BB;Sabatini BL;Lowell BB
通讯作者：
Lowell BB
影响因子：
5.3
作者：
Kurrasch, Deborah M.;Cheung, Clement C.;Ingraham, Holly A.
通讯作者：
Ingraham, Holly A.
影响因子：
7.7
作者：
Burcelin, R;Thorens, B
通讯作者：
Thorens, B
影响因子：
4.8
作者：
Collodet, Caterina;Foretz, Marc;Sakamoto, Kei
通讯作者：
Sakamoto, Kei