Cardiovascular Medicine, Human Physiology and Centre for Neuroscience, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
J Comp Neurol. 2018 Nov 1;526(16):2665-2682. doi: 10.1002/cne.24523. Epub 2018 Oct 18.
Low blood glucose activates brainstem adrenergic and cholinergic neurons, driving adrenaline secretion from the adrenal medulla and glucagon release from the pancreas. Despite their roles in maintaining glucose homeostasis, the distributions of insulin-responsive adrenergic and cholinergic neurons in the medulla are unknown. We fasted rats overnight and gave them insulin (10 U/kg i.p.) or saline after 2 weeks of handling. Blood samples were collected before injection and before perfusion at 90 min. We immunoperoxidase-stained transverse sections of perfused medulla to show Fos plus either phenylethanolamine N-methyltransferase (PNMT) or choline acetyltransferase (ChAT). Insulin injection lowered blood glucose from 4.9 ± 0.3 mmol/L to 1.7 ± 0.2 mmol/L (mean ± SEM; n = 6); saline injection had no effect. In insulin-treated rats, many PNMT-immunoreactive C1 neurons had Fos-immunoreactive nuclei, with the proportion of activated neurons being highest in the caudal part of the C1 column. In the rostral ventrolateral medulla, 33.3% ± 1.4% (n = 8) of C1 neurons were Fos-positive. Insulin also induced Fos in 47.2% ± 2.0% (n = 5) of dorsal medullary C3 neurons and in some C2 neurons. In the dorsal motor nucleus of the vagus (DMV), insulin evoked Fos in many ChAT-positive neurons. Activated neurons were concentrated in the medial and middle regions of the DMV beneath and just rostral to the area postrema. In control rats, very few C1, C2, or C3 neurons and no DMV neurons were Fos-positive. The high numbers of PNMT-immunoreactive and ChAT-immunoreactive neurons that express Fos after insulin treatment reinforce the importance of these neurons in the central response to a decrease in glucose bioavailability.
低血糖会激活脑干肾上腺素能和胆碱能神经元，促使肾上腺髓质释放肾上腺素，胰腺释放胰高血糖素。尽管它们在维持血糖稳态方面发挥着作用，但在髓质中，对胰岛素反应的肾上腺素能和胆碱能神经元的分布尚不清楚。我们让大鼠禁食过夜，在处理 2 周后给它们腹腔内注射胰岛素（10 U/kg）或生理盐水。在注射前和 90 分钟灌注前采集血样。我们用免疫过氧化物酶法对灌注后的髓质横切片进行染色，以显示 Fos 加上苯乙醇胺 N-甲基转移酶（PNMT）或胆碱乙酰转移酶（ChAT）。胰岛素注射使血糖从 4.9±0.3 mmol/L 降至 1.7±0.2 mmol/L（平均值±SEM；n=6）；生理盐水注射则没有影响。在胰岛素处理的大鼠中，许多 PNMT 免疫反应性 C1 神经元具有 Fos 免疫反应性核，激活神经元的比例在 C1 柱的尾部最高。在腹外侧延髓，33.3%±1.4%（n=8）的 C1 神经元呈 Fos 阳性。胰岛素还诱导了 47.2%±2.0%（n=5）的背侧延髓 C3 神经元和一些 C2 神经元中的 Fos。在迷走神经背核（DMV）中，胰岛素引起许多 ChAT 阳性神经元中的 Fos。激活的神经元集中在 DMV 的内侧和中间区域，位于后穹窿下方和稍前方。在对照大鼠中，C1、C2 或 C3 神经元和 DMV 神经元很少有 Fos 阳性。在胰岛素处理后表达 Fos 的大量 PNMT 免疫反应性和 ChAT 免疫反应性神经元，强调了这些神经元在葡萄糖生物利用度降低时对中枢反应的重要性。
