Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia

Inactivation of the DMH selectively inhibits the ACTH and corticosterone responses to hypoglycemia
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DOI:
10.1152/ajpregu.00328.2003
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发表时间:
2004-01-01
影响因子:
2.8
通讯作者:
Figlewicz, DP
Figlewicz, DP
中科院分区:
医学3区
文献类型:
--
作者:
Evans, SB;Wilkinson, CW;Figlewicz, DP

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我们以前曾报道,反复发作的胰岛素诱导的低血糖(IIH)在大鼠的结果在钝化激活的室旁核,弓状核,和背内侧下丘脑(DMH)核。由于DMH激活与交感肾上腺和下丘脑-垂体-肾上腺(HPA)对应激源的反应有关,我们假设其钝化激活可能在反复发作的IIH中也观察到的受损的反调节反应中发挥作用。在本研究中,我们评估了正常DMH激活在对单次IIH的反调节反应中的作用。局部输注利多卡因(n = 8),以抑制DMH在2小时回合的IIH导致一个显着的整体下降的ACTH反应和延迟的皮质酮反应的发作相比,赋形剂输注对照组(n = 9)。我们观察到ACTH反应在时间(t)= 90和120 min时受到抑制(分别为对照水平的50 +/- 12和63 +/-6%),皮质酮反应在t = 30 min时受到早期抑制(对照水平的59 +/- 13%)。肾上腺素、去甲肾上腺素和胰高血糖素的反应不受DMH失活的影响。我们的研究结果表明,DMH失活可能在减少反复发作的IIH后HPA轴的反应发挥了特定的作用。
We have previously reported that repeated bouts of insulin-induced hypoglycemia (IIH) in the rat result in blunted activation of the paraventricular, arcuate, and dorsomedial hypothalamic (DMH) nuclei. Because DMH activation has been implicated in the sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to stressors, we hypothesized that its blunted activation may play a role in the impaired counterregulatory response that is also observed with repeated bouts of IIH. In the present study, we evaluated the role of normal DMH activation in the counterregulatory response to a single bout of IIH. Local infusion of lidocaine (n = 8) to inactivate the DMH during a 2-h bout of IIH resulted in a significant overall decrease of the ACTH response and a delay of onset of the corticosterone response compared with vehicle-infused controls (n = 9). We observed suppression of the ACTH response at time (t) = 90 and 120 min (50 +/- 12 and 63 +/- 6%, respectively, of control levels) and early suppression of the corticosterone response at t = 30 min (59 +/- 13% of the control level). The epinephrine, norepinephrine, and glucagon responses were not altered by DMH inactivation. Our finding suggests that DMH inactivation may play a specific role in decreasing the HPA axis response after repeated bouts of IIH.