Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon "resistance".
Development of insulin and glucagon binding and the adenylate cyclase response in liver membranes of the prenatal, postnatal, and adult rat: evidence of glucagon "resistance".
复制标题
产前、产后和成年大鼠肝膜中胰岛素和胰高血糖素结合的发展和腺苷酸环化酶反应：胰高血糖素“抵抗”的证据。
作者：
E. Blázquez;B. Rubalcava;R. Montesano;L. Orci;R. Unger
尽管大鼠胎仔的血浆胰高血糖素水平在成人范围内，但胎仔中肝糖原的丰度远高于成人。为了解释这一矛盾，腺苷酸环化酶对胰高血糖素的反应进行了研究，在部分纯化的膜大鼠肝脏获得整个围产期生活和3个月的年龄。腺苷酸环化酶对胰高血糖素（10（-9）M）的反应在胎儿生命的第15天仅为成人反应的7%，在第21天为20%。直到产后30天后才达到成熟。然而，腺苷酸环化酶对氟化钠刺激的反应与整个胎儿期的成人反应相当。这些膜制剂对[125 I]碘胰高血糖素（2 × 10（-9）M）的结合在胎儿生命的第15天仅为成人水平的1%，在第21天增加到23%，并且，像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。相反，妊娠第15天的胰岛素结合率为成人水平的11%，第21天为成人水平的45%，出生后第30天达到成人水平。增加膜相关颗粒，反映膜内蛋白，在产前生活中观察到，但平均颗粒数每mum 2达到成人水平的第21天的胎儿生命，表明随后的变化，激素结合明显独立的非特异性变化的颗粒数量。研究结果表明，胎儿肝脏对胰高血糖素作用的敏感性低于成人肝脏，这种胰高血糖素“抵抗”是由肝细胞结合胰高血糖素的能力降低介导的，此时胰岛素的大量结合是可证实的。对胰高血糖素的选择性歧视可能在促进正常胎儿发育所需的合成代谢过程中很重要。
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.