Blazquez E, Rubalcava B, Montesano R, Orci L, Unger R H
Endocrinology. 1976 Apr;98(4):1014-23. doi: 10.1210/endo-98-4-1014.
Although plasma glucagon levels in the rat fetus are in the adult range, hepatic glycogen is present in far greater abundance in the fetus than in the adult. To explain this paradox, adenylate cyclase response to glucagon was studied in partially purified membranes of rat livers obtained throughout perinatal life and at 3 months of age. The adenylate cyclase response to glucagon (10(-9) M) was only 7% of the adult response at day 15 of fetal life and 20% on the 21st day. No until after the 30th day postpartum did not reach maturity. Yet, the adenylate cyclase response to stimulation by NaF was comparable to the adult response throughout fetal life. The binding of [125I]iodoglucagon (2 X 10(-9) M) by these membrane preparations was only 1% of the adult level at day 15 of fetal life and increased to 23% at the 21st day, and, like the adenylate cyclase response to glucagon, did not reach maturity until after the 30th day of postnatal life. In contrast, insulin binding on the 15th day of gestation was 11% of the adult level and on the 21st day 45% of the adult level, reaching adult levels by the 30th postnatal day. An increase in membrane-associated particles, reflecting intramembranous protein, was observed during prenatal life, but the mean particle number per mum2 reached adult levels on the 21st day of fetal life, indicating that subsequent changes in hormone binding were clearly independent of non-specific changes in the number of particles. The findings suggest that the fetal liver is less sensitive to glucagon action than the adult liver, and that this glucagon "resistance" is mediated by a reduced capacity of the hepatocyte to bind glucagon at a time when substantial binding of insulin is demonstrable. Selective discrimination against glucagon may be important in promoting the anabolic processes required for normal fetal development.
尽管大鼠胎儿血浆中胰高血糖素水平处于成年大鼠的范围，但胎儿肝脏中的肝糖原含量却远高于成年大鼠。为了解释这一矛盾现象，研究了围产期及3月龄大鼠肝脏部分纯化膜中腺苷酸环化酶对胰高血糖素的反应。在胎儿期第15天，腺苷酸环化酶对胰高血糖素（10⁻⁹M）的反应仅为成年反应的7%，在第21天为20%。直到产后第30天才达到成熟水平。然而，在整个胎儿期，腺苷酸环化酶对氟化钠刺激的反应与成年反应相当。这些膜制剂对[¹²⁵I]碘胰高血糖素（2×10⁻⁹M）的结合在胎儿期第15天仅为成年水平的1%，在第21天增加到23%，并且与腺苷酸环化酶对胰高血糖素的反应一样，直到出生后第30天才达到成熟水平。相比之下，妊娠第15天胰岛素结合为成年水平的11%，第21天为45%，到出生后第30天达到成年水平。在产前观察到反映膜内蛋白质的膜相关颗粒增加，但在胎儿期第21天每μm²的平均颗粒数达到成年水平，这表明随后激素结合的变化显然与颗粒数量的非特异性变化无关。这些发现表明，胎儿肝脏对胰高血糖素作用的敏感性低于成年肝脏，并且这种胰高血糖素“抵抗”是由肝细胞在胰岛素大量结合时结合胰高血糖素的能力降低所介导的。对胰高血糖素的选择性区分可能对促进正常胎儿发育所需的合成代谢过程很重要。
