中枢型糖皮质激素受体对雄性大鼠下丘脑腹内侧核糖原代谢酶和糖调节神经递质标记蛋白表达的调节。

Abdulrahman Alhamyani, A S M Hasan Mahmood, Ayed Alshamrani, Mostafa M H Ibrahim, Karen P Briski
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引用次数: 0

摘要

下丘脑腹内侧核(VMN)葡萄糖调节神经递质γ-氨基丁酸(GABA)和一氧化氮(NO)信号在糖原动员中的调节。糖皮质激素控制星形胶质细胞糖原代谢。经典的(II型)糖皮质激素受体(GR)在控制葡萄糖稳态的关键脑结构中表达,包括VMN。目前的研究提出了前脑GR对VMN糖原合成酶(GS)和磷酸化酶(GP)蛋白表达的调节与糖调节传递的控制相关的假设。雄性大鼠组在胰岛素诱导的低血糖(IIH)发生前,采用脑室内(icv)给药GR拮抗剂RU486或对照剂预处理,或在皮下注射胰岛素稀释剂前,采用地塞米松(DEX)或对照剂预处理。DEX增加VMN、GS和去甲肾上腺素敏感gp -肌型(GPmm)表达,但不改变代谢缺陷敏感gp -脑型(gbb)表达。RU486在IIH期间增强了GS和gbb谱。DEX或RU486分别上调正常血糖和低血糖动物的VMN星形胶质细胞(MCT1)和神经元(MCT2)单羧酸转运蛋白谱。谷氨酸脱羧酶65/67和神经元一氧化氮合酶(nNOS)蛋白均增加,而RU486增强了低血糖nNOS的表达模式。结果表明,GR对VMN GS、MCT1/2和nNOS蛋白在促(促)低血糖和抑(抑)低血糖时的影响存在差异;这些发现表明,一氧化氮传递的上调可能在一定程度上反映了葡萄糖融入糖原和/或组织乳酸需求的增加。数据还提供了代谢状态依赖性GR调控VMN GPmm和GPbb谱的新证据;因此,代谢稳定性的GABA信号可能部分反映了在高血糖和低血糖期间刺激特异性糖原分解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Central Type II Glucocorticoid Receptor Regulation of Ventromedial Hypothalamic Nucleus Glycogen Metabolic Enzyme and Glucoregulatory Neurotransmitter Marker Protein Expression in the Male Rat.

The ventromedial hypothalamic nucleus (VMN) glucoregulatory neurotransmitters γ-aminobutyric acid (GABA) and nitric oxide (NO) signal adjustments in glycogen mobilization. Glucocorticoids control astrocyte glycogen metabolism in vitro. The classical (type II) glucocorticoid receptor (GR) is expressed in key brain structures that govern glucostasis, including the VMN. Current research addressed the hypothesis that forebrain GR regulation of VMN glycogen synthase (GS) and phosphorylase (GP) protein expression correlates with control of glucoregulatory transmission. Groups of male rats were pretreated by intracerebroventricular (icv) delivery of the GR antagonist RU486 or vehicle prior to insulin-induced hypoglycemia (IIH), or were pretreated icv with dexamethasone (DEX) or vehicle before subcutaneous insulin diluent injection. DEX increased VMN GS and norepinephrine-sensitive GP-muscle type (GPmm), but did not alter metabolic deficit-sensitive GP-brain type (GPbb) expression. RU486 enhanced GS and GPbb profiles during IIH. VMN astrocyte (MCT1) and neuronal (MCT2) monocarboxylate transporter profiles were up-regulated in euglycemic and hypoglycemic animals by DEX or RU486, respectively. Glutamate decarboxylase65/67 and neuronal nitric oxide synthase (nNOS) proteins were both increased by DEX, yet RU486 augmented hypoglycemic nNOS expression patterns. Results show that GR exert divergent effects on VMN GS, MCT1/2, and nNOS proteins during eu- (stimulatory) versus hypoglycemia (inhibitory); these findings imply that up-regulated NO transmission may reflect, in part, augmented glucose incorporation into glycogen and/or increased tissue lactate requirements. Data also provide novel evidence for metabolic state-dependent GR regulation of VMN GPmm and GPbb profiles; thus, GABA signaling of metabolic stability may reflect, in part, stimulus-specific glycogen breakdown during eu- versus hypoglycemia.

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