PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat
PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat
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DOI：
10.1152/ajpregu.2001.281.5.r1426
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发表时间：
2001-11-01
影响因子：
2.8
通讯作者：
Figlewicz, DP
中科院分区：
文献类型：
--
作者：
Evans, SB;Wilkinson, CW;Figlewicz, DP
低血糖相关自主神经功能衰竭（HAAF）的潜在机制尚不清楚。为了检验参与对低血糖的反调节反应的脑区域的激活被HAAF钝化的假设，在2天的方案中对大鼠进行了研究。在第2天胰岛素诱导的低血糖（0.5 U胰岛素）期间测量神经内分泌反应和脑激活（c-Fos免疫反应性）。100 g体重（-1）。h（-1）iv，持续2 h）。Hypo-Hypo动物表现出HAAF，肾上腺素、胰高血糖素和皮质酮（Cort）反应减弱，内侧下丘脑[室旁核（PVN）、背内侧核（DMH）和弓状核（Arc）]激活减少。为了评估第1天Cort增加是否是下丘脑激活减少的原因，在第1天侧脑室内输注Cort（72 μ g），并测量对第2天低血糖的反应。脑室内Cort输注未能改变对第2天低血糖的神经内分泌反应，尽管中枢神经系统和外周Cort水平均升高。然而，第1天Cort在两个与Hypo-Hypo相同的下丘脑区域（DMH和Arc）中减弱了反应，但在PVN中没有。这些结果表明，减少激活的PVN可能是重要的HAAF的发展和前期暴露于高水平的Cort并不总是足以产生HAAF。
The mechanism(s) underlying hypoglycemia-associated autonomic failure (HAAF) are unknown. To test the hypothesis that the activation of brain regions involved in the counterregulatory response to hypoglycemia is blunted with HAAF, rats were studied in a 2-day protocol. Neuroendocrine responses and brain activation (c-Fos immunoreactivity) were measured during day 2 insulin-induced hypoglycemia (0.5 U insulin . 100 g body wt(-1) . h(-1) iv for 2 h) after day 1 hypoglycemia (Hypo-Hypo) or vehicle. Hypo-Hypo animals demonstrated HAAF with blunted epinephrine, glucagon, and corticosterone (Cort) responses and decreased activation of the medial hypothalamus [the paraventricular (PVN), dorsomedial (DMH), and arcuate (Arc) nuclei]. To evaluate whether increases in day 1 Cort were responsible for the decreased hypothalamic activation, Cort was infused intracerebroventricularly (72 mug) on day 1 and the response to day 2 hypoglycemia was measured. Intracerebroventricular Cort infusion failed to alter the neuroendocrine response to day 2 hypoglycemia, despite elevating both central nervous system and peripheral Cort levels. However, day 1 Cort blunted responses in two of the same hypothalamic regions as Hypo-Hypo (the DMH and Arc) but not in the PVN. These results suggest that decreased activation of the PVN may be important in the development of HAAF and that antecedent exposure to elevated levels of Cort is not always sufficient to produce HAAF.