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新生大鼠的血浆氨基酸水平与肝糖异生的发育

Plasma amino acid levels and development of hepatic gluconeogenesis in the newborn rat.

作者信息

Girard J R, Guillet I, Marty J, Marliss E B

出版信息

Am J Physiol. 1975 Aug;229(2):466-73. doi: 10.1152/ajplegacy.1975.229.2.466.

Abstract

The metabolism of endogenous and exogenous amino acids has been characterized during a 16-h fast after birth in the rat. Eighteen of 22 amino acids showed a decrease in plasma concentration up to 16 h, the most profound and sustained changes affecting those quantitatively important in gluconeogenesis. The hepatic accumulation of injected [14C]aminoisobutyric acid showed a progressive rise after birth. The in vivo conversion of 14C-labeled lactate, alanine, serine, and glutamine to [14C]glucose increased for 6 h, but all except glutamine showed a decline by 16 h. The in vitro conversion of several gluconeogenic substrates (10mM), however, increased with time in each instance. These data confirm that the capacity for hepatic gluconeogenesis and maintenance of blood glucose concentration appears immediately after birth. Nevertheless, profound hypoglycemia recurs at 16 h and responds only minimally and transiently to exogenous gluconeogenic substrate loads. In contrast, the fed newborn maintains normoglycemia, higher endogenous amino acid levels, and the capacity for substrate conversion at this time. The mechanism for stimulation of hepatic gluconeogenic pathways thus is present in both fasted and fed neonatal rats. However, owing to insufficient energy sources to sustain gluconeogenesis and to inadequate gluconeogenic substrate, the rat is unable to maintain normoglycemia if fasted 16 h.

摘要

在大鼠出生后的16小时禁食期间,对内源性和外源性氨基酸的代谢进行了表征。22种氨基酸中有18种在长达16小时内血浆浓度下降,最显著且持续的变化影响那些在糖异生中数量上重要的氨基酸。注射的[14C]氨基异丁酸在肝脏中的积累在出生后呈逐渐上升趋势。14C标记的乳酸、丙氨酸、丝氨酸和谷氨酰胺向[14C]葡萄糖的体内转化在6小时内增加,但除谷氨酰胺外,所有其他氨基酸在16小时时均呈下降趋势。然而,在每种情况下,几种糖异生底物(10mM)的体外转化均随时间增加。这些数据证实,肝脏糖异生能力和维持血糖浓度的能力在出生后立即出现。尽管如此,在16小时时会再次出现严重低血糖,对外源性糖异生底物负荷的反应仅为轻微且短暂的。相比之下,此时进食的新生大鼠维持正常血糖水平、较高的内源性氨基酸水平以及底物转化能力。因此,禁食和进食的新生大鼠均存在刺激肝脏糖异生途径的机制。然而,由于维持糖异生的能量来源不足以及糖异生底物不足,如果禁食16小时,大鼠无法维持正常血糖水平。

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