VENTROMEDIAL HYPOTHALAMIC-LESIONS IN RATS SUPPRESS COUNTERREGULATORY RESPONSES TO HYPOGLYCEMIA
VENTROMEDIAL HYPOTHALAMIC-LESIONS IN RATS SUPPRESS COUNTERREGULATORY RESPONSES TO HYPOGLYCEMIA
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DOI：
10.1172/jci117150
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发表时间：
1994-04-01
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, WP;DURING, MJ;SHULMAN, GI
在低血糖时，中枢神经系统参与了反调节激素释放的激活。然而，涉及的确切基因座还没有确定。为了确定下丘脑腹内侧核(VMH)在低血糖激素反应中的作用，我们在清醒的SpragueDawley大鼠上进行了降糖钳夹实验，这些大鼠的双侧VMH损伤是由局部注射鹅膏油酸造成的。下丘脑外侧区、额叶损毁大鼠、假手术大鼠(不注射立体定向针入下丘脑)和幼稚动物作为对照组。夹具研究分为两个阶段。在第一个小时内，通过变量葡萄糖输注将血糖固定在正常血糖水平(类似于5.9 mM)。此后，在额外的90分钟内，允许葡萄糖降至(A)轻度低血糖(类似于3.0 mM)或(B)更严重的低血糖(类似于2.5 mM)。在每个低血糖平台上，下丘脑外侧区、额叶受损、假手术和幼稚动物的胰高血糖素和儿茶酚胺反应几乎相同。相反，VMH大鼠的胰升糖素、肾上腺素和去甲肾上腺素反应明显受到抑制；与其他组相比，轻度低血糖时激素减少50-60%，重度低血糖时激素减少75%-80%。我们的结论是，VMH在低血糖时触发胰高血糖素和儿茶酚胺的释放起着至关重要的作用。
The central nervous system has been implicated in the activation of counterregulatory hormone release during hypoglycemia. However, the precise loci involved are not established. To determine the role of the ventromedial hypothalamic nuclei (VMH) in the hormonal response to hypoglycemia, we performed hypoglycemic clamp studies in conscious Sprague-Dawley rats with bilateral VMH lesions produced by local ibotenic acid injection 2 wk earlier. Rats with lesions in the lateral hypothalamic area, frontal lobe, sham operated (stereotaxic needle placement into hypothalamus without injection), and naive animals served as control groups. The clamp study had two phases. For the first hour plasma glucose was fixed by a variable glucose infusion at euglycemia (similar to 5.9 mM). Thereafter, for an additional 90 min, glucose was either allowed to fall to (a) mild hypoglycemia (similar to 3.0 mM) or (b) more severe hypoglycemia (similar to 2.5 mM). Glucagon and catecholamine responses of lateral hypothalamic area-, frontal lobe-lesioned, sham operated, and naive animals were virtually identical at each hypoglycemic plateau. In contrast, glucagon, epinephrine, and norepinephrine responses in the VMH-lesioned rats were markedly inhibited; hormones were diminished by 50-60% during mild and by 75-80% during severe hypoglycemia as compared with the other groups. We conclude that the VMH plays a crucial role in triggering the release of glucagon and catecholamines during hypoglycemia.