Brain glycogen is a vital energy source during metabolic imbalance. Metabolic sensory neurons in the ventromedial hypothalamic nucleus (VMN) shape glucose counter-regulation. Insulin-induced hypoglycemic (IIH) male rats were infused icv with the glycogen breakdown inhibitor CP-316,819 (CP) to investigate whether glycogen-derived fuel controls basal and/or hypoglycemic patterns of VMN gluco-regulatory neuron energy stability and transmitter signaling. CP caused dose-dependent amplification of basal VMN glycogen content and either mobilization (low dose) or augmentation (high dose) of this depot during IIH. Drug treatment also prevented hypoglycemic diminution of tissue glucose in multiple structures. Low CP dose caused IIH-reversible augmentation of AMPK activity and glutamate decarboxylase (GAD) protein levels in laser-microdissected VMN GABA neurons, while the higher dose abolished hypoglycemic adjustments in these profiles. VMN steroidogenic factor-1 (SF-1) neurons exhibited suppressed (low CP dose) or unchanged (high CP dose) basal SF-1 expression and AMPK refractoriness of hypoglycemia at each dose. CP caused dose-proportionate augmentation of neuronal nitric oxide synthase protein and enhancement (low dose) or diminution (high dose) of this profile during IIH; AMPK activity in these cells was decreased in high dose-pretreated IIH rats. CP exerted dose-dependent effects on basal and hypoglycemic patterns of glucagon, but not corticosterone secretion. Results verify that VMN GABA, SF-1, and nitrergic neurons are metabolic sensory in function and infer that these populations may screen unique aspects of neurometabolic instability. Correlation of VMN glycogen augmentation with attenuated hypoglycemic VMN gluco-regulatory neuron AMPK activity implies that expansion of this fuel reservoir preserves cellular energy stability during this metabolic threat.

中文翻译：

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脑室内糖原磷酸化酶抑制剂CP-316,819的输注对雄性大鼠下丘脑糖原含量，代谢神经元AMPK活性和神经递质表达的影响。

脑糖原是代谢失衡过程中的重要能源。下丘脑下丘脑核（VMN）中的代谢感觉神经元对葡萄糖的反调节作用。icv注射胰岛素诱导的降血糖（IIH）雄性大鼠 与糖原分解抑制剂CP-316,819（CP）一起研究了糖原衍生的燃料是否控制VMN葡萄糖调节神经元能量稳定性和发射信号的基础和/或降血糖模式。CP导致基础VMN糖原含量的剂量依赖性扩增以及IIH期间该贮库的动员（低剂量）或增强（高剂量）。药物治疗还可以防止多种结构中组织葡萄糖的降血糖减少。低CP剂量导致激光显微切割的VMN GABA神经元中IIH可逆的AMPK活性和谷氨酸脱羧酶（GAD）蛋白水平增加，而较高的剂量则取消了这些谱图中的降血糖调节。VMN类固醇生成因子1（SF-1）神经元在每个剂量下均表现出抑制的（低CP剂量）或不变的（高CP剂量）基础SF-1表达以及低血糖的AMPK难治性。在IIH期间，CP引起神经元一氧化氮合酶蛋白的剂量成比例增加，并且该分布图的增强（低剂量）或减少（高剂量）；在高剂量预处理的IIH大鼠中，这些细胞中的AMPK活性降低。CP对胰高血糖素的基础和降血糖模式具有剂量依赖性，但对皮质酮的分泌没有影响。结果证实，VMN GABA，SF-1和硝能神经元在功能上具有代谢感觉，并推断这些人群可能筛选出神经代谢不稳定的独特方面。