Metabolic, hormonal, and hemodynamic changes induced by metabotropic excitatory amino acid agonist (1S,3R)-ACPD.
Metabolic, hormonal, and hemodynamic changes induced by metabotropic excitatory amino acid agonist (1S,3R)-ACPD.
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代谢型兴奋性氨基酸激动剂 (1S,3R)-ACPD 引起的代谢、激素和血流动力学变化。
DOI：
10.1152/ajpregu.1995.268.4.r1026
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Ajmal,M
中科院分区：
文献类型：
--
作者：
Lang,CH;Ajmal,M
本研究的目的是确定中枢给药（1 S，3R）-1-氨基环戊烷-1，3-二羧酸（ACPD），一种选择性代谢型谷氨酸受体激动剂，是否会刺激葡萄糖代谢，激活下丘脑-垂体-肾上腺轴，或影响胰腺内分泌。侧脑室注射ACPD在15分钟内使动脉血糖水平增加60%，这在整个3小时的实验方案中持续存在。这种高血糖症是由于早期肝葡萄糖产生（HGP，88%）的增加超过了外周组织葡萄糖摄取的增加（66%）。葡萄糖代谢刺激与血浆胰岛素（145%）和胰高血糖素（3倍）水平的一过性升高以及皮质酮（141%）、肾上腺素（3- 5倍）和去甲肾上腺素（32-110%）的持续升高相关。静脉输注α-和β-肾上腺素能拮抗剂可防止ACPD诱导的葡萄糖代谢增加。ACPD后动脉血压、心脏指数和总外周阻力没有改变。总体而言，局部血流量的变化并不明显，尽管ACPD确实增加了肝脏（2倍）和心脏（48%）的血流量，并减少了胃（33%）的血流量。这些结果表明，中枢给药ACPD 1）增强HGP，这主要是由肾上腺素能刺激介导的; 2）增加外周组织的葡萄糖摄取，这似乎是由高胰岛素血症和高血糖症介导的; 3）刺激胰腺和肾上腺激素分泌，而不依赖于肾上腺素能激活;和4）在局部血流中产生最小的变化，其不能解释由ACPD产生的葡萄糖代谢反应。（250字处删节）
The purpose of the present study was to determine whether central administration of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), a selective metabotropic glutamate receptor agonist, would stimulate glucose metabolism, activate the hypothalamic-pituitary-adrenal axis, or influence pancreatic endocrine secretion. Intracerebroventricular injection of ACPD increased arterial glucose levels by 60% within 15 min, which were sustained throughout the 3-h experimental protocol. This hyperglycemia resulted from an early increase in hepatic glucose production (HGP, 88%) that exceeded the increase in glucose uptake by peripheral tissues (66%). Stimulation of glucose metabolism was associated with transient elevations in plasma insulin (145%) and glucagon (3-fold) levels and more sustained elevations in corticosterone (141%), epinephrine (3- to 5-fold), and norepinephrine (32-110%). Intravenous infusion of alpha- and beta-adrenergic antagonists prevented the ACPD-induced increase in glucose metabolism. Arterial blood pressure, cardiac index, and total peripheral resistance were not altered after ACPD. Overall, the changes in regional blood flow were unremarkable, although ACPD did increase blood flow to the liver (2-fold) and heart (48%) and decrease flow to the stomach (33%). These results indicate that central administration of ACPD 1) enhances HGP, which is primarily mediated by adrenergic stimulation; 2) increases glucose uptake by peripheral tissues, which appears to be mediated by both hyperinsulinemia and hyperglycemia; 3) stimulates pancreatic and adrenal hormone secretion independent of adrenergic activation; and 4) produces minimal changes in regional blood flow that cannot explain the glucose metabolic response produced by ACPD.(ABSTRACT TRUNCATED AT 250 WORDS)