Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats
Local ventromedial hypothalamus glucose perfusion blocks counterregulation during systemic hypoglycemia in awake rats
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DOI：
10.1172/jci119165
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发表时间：
1997-01-15
影响因子：
15.9
通讯作者：
Shulman, GI
中科院分区：
文献类型：
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作者：
Borg, MA;Sherwin, RS;Shulman, GI
下丘脑腹内侧核（VMH）是低血糖综合激素反应所必需的。为了确定VMH作为葡萄糖传感器的作用，我们进行了旨在专门防止VMH中的血糖减少的实验，同时在其他地方产生低血糖。我们使用清醒的长期插管大鼠，其中局部VMH葡萄糖灌注（100 mM或15 mM的D-葡萄糖）与连续的正常血糖-低血糖钳夹相结合。在两个对照组中，VMH灌注（a）缺乏葡萄糖的等渗溶液，或（B）非代谢性L-葡萄糖（100 mM）。在全身性低血糖期间，在用100 mM L-葡萄糖或缺乏葡萄糖的等渗溶液灌注的对照动物中，胰高血糖素和儿茶酚胺浓度迅速增加。与此相反，胰高血糖素，肾上腺素和去甲肾上腺素的释放被抑制的动物中，VMH灌注D-葡萄糖;激素分泌部分抑制VMH灌注15 mM D-葡萄糖和抑制类似的85%时，VMH灌注100 mM D-葡萄糖，与对照组相比。我们的结论是，VMH必须感觉到低血糖的充分激活的儿茶酚胺和胰高血糖素分泌，它是一个关键的葡萄糖传感器低血糖的反调节。
The ventromedial hypothalamic nucleus (VMH) is necessary for the integrated hormonal response to hypoglycemia. To determine the role of the VMH as a glucose sensor, we performed experiments designed to specifically prevent glucopenia in the VMH, while producing hypoglycemia elsewhere. We used awake chronically catheterized rats, in which local VMH glucose perfusion (100 mM or 15 mM of D-glucose) was combined with a sequential euglycemichypoglycemic clamp. In two control groups the VMH was perfused either with (a) an iso-osmotic solution lacking glucose, or with (b) nonmetabolizable L-glucose (100 mM). During systemic hypoglycemia glucagon and catecholamine concentrations promptly increased in the control animals perfused with either 100 mM L-glucose or the iso-osmotic solution lacking glucose. In contrast, glucagon, epinephrine and norepinephrine release was inhibited in the animals in which the VMH was perfused with D-glucose; hormonal secretion was partially suppressed by the VMH perfusion with 15 mM D-glucose and suppressed by similar to 85% when the VMH was perfused with 100 mM D-glucose, as compared with the control groups. We conclude that the VMH must sense hypoglycemia for full activation of catecholamine and glucagon secretion and that it is a key glucose sensor for hypoglycemic counterregulation.