FUELS, HORMONES, AND LIVER METABOLISM AT TERM AND DURING EARLY POSTNATAL-PERIOD IN RAT

FUELS, HORMONES, AND LIVER METABOLISM AT TERM AND DURING EARLY POSTNATAL-PERIOD IN RAT
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DOI:
10.1172/jci107519
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发表时间:
1973-01-01
影响因子:
15.9
通讯作者:
ASSAN, R
ASSAN, R
中科院分区:
医学1区
文献类型:
--
作者:
GIRARD, JR;CUENDET, GS;ASSAN, R

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在新生大鼠中研究了所有哺乳动物经历的第一次禁食的代谢反应。燃料和激素的水平已经在胎儿和母体循环中进行了比较。然后,在正常出生时间前剖宫产后,在新生儿期的前16小时内对相同参数的连续变化进行量化。不允许摄入热量,新生儿保持在37°C。对参与葡萄糖生成的三种关键肝酶的活性进行了估计,观察到母体和胎儿激素和能量的显著差异。胎仔中葡萄糖、游离脂肪酸和甘油水平较低,但乳酸、α-氨基氮、丙氨酸和谷氨酰胺水平较高。丙酮酸、谷氨酸和酮体无显著差异。一个显着较高的胎儿免疫反应性胰岛素和一个稍低的免疫反应性胰高血糖素(胰腺)的组合,导致在胰岛素-胰高血糖素的比例,在一个有机体在合成代谢状态相一致的发现,在出生时的大鼠提出了一个身体组成相对于燃料可用于动员和转换,这是由碳水化合物和蛋白质为主,因为很少脂肪存在。然而,在出生时发生短暂的低血糖,与胰岛素快速下降和胰高血糖素升高相关,导致胰岛素与胰高血糖素的关系逆转,如在母亲中观察到的比例。经过一段时间后,肝脏磷酸化酶,葡萄糖-6-磷酸酶和磷酸烯醇式丙酮酸羧激酶的活性增加。与这些酶变化同时发生的是,血糖恢复到胎儿水平或高于胎儿水平。有趣的是,在酶活性上升和血糖恢复之前,观察到的致血管紧张素原前体、乳酸和氨基酸水平的下降。然而,4小时后,低血糖复发,在一段时间内降低肝糖原含量和血乳酸,丙酮酸和甘油水平,但稳定或增加的氨基酸浓度。在糖原储备耗尽的这一阶段,肝再生不足以维持正常。脂肪来源的底物显示出较小幅度的早期变化。游离脂肪酸的增加不到出生时的两倍,尽管这种增加持续到6小时。而甘油短暂上升,乙酰乙酸没有变化,β-羟基丁酸浓度下降。两种酮体均在16 h时显著升高。在游离脂肪酸水平降低的时候。血浆生长激素,虽然高于在胎儿比母体循环中,没有表现出一致的变化在观察periods.The出生时的胰腺内分泌激素的水平的变化是适当的时间,幅度和方向牵连作为主要的调节剂的代谢反应在新生儿期的大鼠。
The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 37°C. Activities of three key hepatic enzymes involved in glucose production were estimated.Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, α-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state.The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia.Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and β-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h. at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation.The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.