Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia
Australian School of Advanced Medicine, Macquarie University, Sydney, New South Wales, Australia.
Diabetes. 2014 Jun;63(6):1895-906. doi: 10.2337/db13-1073. Epub 2014 Feb 18.
Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in the release of adrenaline. The current study aimed to establish 1) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release in vivo and 2) whether direct activation by glucoprivation or orexin release in the RVLM modulates the adrenaline release. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic rats. Firstly, inhibition of neurons in the PeH abolished the increase in adrenal sympathetic nerve activity (ASNA) to systemic glucoprivation. Secondly, glucoprivation of neurons in the PeH increased ASNA. Thirdly, in vivo or in vitro glucoprivation did not affect the activity of RVLM adrenal premotor neurons. Finally, blockade of orexin receptors in the RVLM abolished the increase in ASNA to neuroglucoprivation in the PeH. The evoked changes in ASNA were directly correlated to levels of plasma metanephrine but not to normetanephrine. These findings suggest that orexin release modulates the activation of adrenal presympathetic neurons in the RVLM.
糖剥夺激活了穹窿周下丘脑（PeH）和延髓头端腹外侧区（RVLM）中的神经元，导致肾上腺素释放。本研究旨在确定：1）PeH 或 RVLM 中的神经糖剥夺是否会在体内引发肾上腺素释放；2）RVLM 中糖剥夺或食欲素释放的直接激活是否会调节肾上腺素释放。在麻醉、血糖正常的大鼠中，通过微注射 2-脱氧-D-葡萄糖或 5-硫代-D-葡萄糖来引发 PeH 或 RVLM 中的神经糖剥夺。首先，PeH 神经元的抑制消除了全身糖剥夺引起的肾上腺交感神经活动（ASNA）增加。其次，PeH 神经元的糖剥夺增加了 ASNA。第三，体内或体外糖剥夺均不影响 RVLM 肾上腺运动前神经元的活性。最后，RVLM 中食欲素受体的阻断消除了 PeH 中神经糖剥夺引起的 ASNA 增加。ASNA 的诱发变化与血浆甲氧基肾上腺素水平直接相关，但与去甲肾上腺素无关。这些发现表明，食欲素释放调节 RVLM 中肾上腺节前神经元的激活。
