Jame P, Ktorza A, Bihoreau M T, Nurjhan N, Ferré P, Girard J, Picon L
Laboratoire de Physiologie du Développement, URA CNRS 307, Université Paris, France.
Pediatr Res. 1990 Dec;28(6):646-51. doi: 10.1203/00006450-199012000-00021.
We have investigated the respective roles of insulin and glucagon in the initiation of hepatic glycogen degradation during the early postnatal period in rats, with special regard on the inhibitory effect of insulin on this process. Pregnant rats were rendered either slightly (8.5 mM) or highly hyperglycemic (22 mM) by infusing glucose during the last week of pregnancy. Fasted, newborn rats were studied from delivery to 16 h postpartum. At birth, newborns from slightly hyperglycemic rats showed higher glycemia and insulinemia and lower plasma glucagonemia compared with controls. Newborns from highly hyperglycemic rats were still more hyperglycemic and exhibited low plasma glucagon concentrations, but they were not hyperinsulinemic. In control newborns, hepatic glycogen breakdown was triggered by 2 h after delivery. By contrast, hyperglycemic-hyperinsulinemic newborns (newborns from slightly hyperglycemic rats) were unable to mobilize liver glycogen before 8-10 h after delivery. In hyperglycemic-normoinsulinemic newborns (newborns from highly hyperglycemic rats), hepatic glycogen concentration significantly started to decline 2 h after delivery and was no longer different from controls at 8 h. Anti-insulin serum injection at delivery promoted a prompt decrease in liver glycogen stores in controls as well as in newborns from slightly hyperglycemic rats. Phosphorylase a/synthase a ratio rose rapidly after delivery in controls and in newborns from highly hyperglycemic rats (maximum 4 h), whereas in newborns from slightly hyperglycemic rats, it rose much more slowly than in the two other groups (maximum 16 h). These data suggest that, in newborns from hyperglycemic mothers, hyperinsulinemia during late fetal and early neonatal life is the main factor preventing postnatal hepatic glycogenolysis.
我们研究了胰岛素和胰高血糖素在大鼠出生后早期肝糖原降解起始过程中的各自作用，特别关注胰岛素对该过程的抑制作用。在妊娠最后一周通过输注葡萄糖使孕鼠处于轻度（8.5 mM）或高度高血糖状态（22 mM）。对禁食的新生大鼠从出生到出生后16小时进行研究。出生时，与对照组相比，轻度高血糖孕鼠的新生鼠血糖和胰岛素水平较高，血浆胰高血糖素水平较低。高度高血糖孕鼠的新生鼠血糖更高，血浆胰高血糖素浓度较低，但它们并非高胰岛素血症。在对照新生鼠中，出生后2小时开始触发肝糖原分解。相比之下，高血糖 - 高胰岛素血症新生鼠（轻度高血糖孕鼠的新生鼠）在出生后8 - 10小时之前无法动员肝糖原。在高血糖 - 正常胰岛素血症新生鼠（高度高血糖孕鼠的新生鼠）中，出生后2小时肝糖原浓度显著开始下降，8小时时与对照组无差异。出生时注射抗胰岛素血清促进了对照组以及轻度高血糖孕鼠新生鼠肝脏糖原储备的迅速减少。对照组和高度高血糖孕鼠新生鼠出生后磷酸化酶a/合成酶a比值迅速升高（最大4小时），而轻度高血糖孕鼠新生鼠的升高速度比其他两组慢得多（最大16小时）。这些数据表明，在高血糖母亲的新生鼠中，胎儿晚期和新生儿早期的高胰岛素血症是防止出生后肝糖原分解的主要因素。
