Hanson R W, Ballard J
Fed Proc. 1975 Feb;34(2):166-71.
Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of CAMP.
大鼠肝脏的糖异生直到出生时才开始。磷酸烯醇式丙酮酸羧激酶最初在出生时出现，是糖异生序列中最后一个发育的酶。这种酶在大鼠肝脏细胞质中的出现是由酶合成的刺激引起的，可能直接归因于肝脏中cAMP浓度的增加。酶降解直到出生后36小时才开始。对子宫内胎鼠的研究表明，二丁酰cAMP或胰高血糖素会刺激磷酸烯醇式丙酮酸羧激酶的合成，并且这种作用可被胰岛素阻断。已知胰岛素会抑制成年大鼠肝脏和培养的鲁伯H-35肝细胞中磷酸烯醇式丙酮酸羧激酶的合成。糖皮质激素对胎鼠肝脏中该酶的合成没有影响。吉拉德等人（《临床研究杂志》52: 3190, 1973）的研究证实，胰岛素与胰高血糖素的摩尔比在出生后立即从10降至1小时后的1。这是由于出生时胰高血糖素升高和胰岛素浓度下降所致。这些研究，连同我们关于磷酸烯醇式丙酮酸羧激酶合成的研究，表明胰岛素浓度的急剧下降可能解除对酶合成的正常抑制。这将使得胰高血糖素介导的CAMP浓度升高对酶合成产生初始刺激作用。
