MECHANISMS OF CATECHOLAMINE EFFECTS ON KETOGENESIS
MECHANISMS OF CATECHOLAMINE EFFECTS ON KETOGENESIS
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DOI：
10.1152/ajpendo.1984.247.2.e173
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发表时间：
1984-01-01
影响因子：
--
通讯作者：
ALBERTI, KGMM
中科院分区：
文献类型：
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作者：
BAHNSEN, M;BURRIN, JM;ALBERTI, KGMM
生酮作用可以在几个部位受到控制。第一步是脂解，释放血浆非酯化脂肪酸（NEFA）底物。血浆NEFA以浓度依赖性方式被肝脏吸收，转化为酰基辅酶A衍生物后，可以被再酯化或通过肉毒碱穿梭进入线粒体。在β-氧化后，所得乙酰辅酶A可转化为酮体，然后释放到循环中，或与草酰乙酸缩合并进入三羧酸循环，第三个潜在控制点。在人体中，输注肾上腺素会导致脂肪酸、甘油和酮体一过性增加2 - 3倍。胰岛素水平显示出小幅绝对增加。去甲肾上腺素也有类似的作用，尽管胰岛素水平往往受到抑制，胰高血糖素水平略有上升。如果同时加入生长抑素，脂解和生酮作用会加重和延长。高剂量的多巴胺单独对酮体没有影响，但在生长抑素存在下，NEFA和酮体略有增加，可能在生酮中起调节作用。因此，儿茶酚胺的生酮作用可能发生在脂肪细胞或肝脏中。对灌注肝脏或肝细胞的研究表明，即使使用超生理剂量的儿茶酚胺，对生酮的影响也很小。此外，大鼠输注研究显示酮生成减少而非增加，NEFA水平无变化。数据表明：a）存在种属差异，B）在人体中，肾上腺素和去甲肾上腺素诱导的生酮增加继发于NEFA底物供应增加。
Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.