Effect of glucagon and insulin on the growth of neonatal rat hepatocytes in primary tissue culture.
Effect of glucagon and insulin on the growth of neonatal rat hepatocytes in primary tissue culture.
复制标题
胰高血糖素和胰岛素对原代组织培养中新生大鼠肝细胞生长的影响。
DOI：
10.1210/endo-102-4-1155
复制
发表时间：
1978
期刊：
影响因子：
4.8
通讯作者：
P. Andreis
中科院分区：
文献类型：
--
作者：
U. Armato;E. Draghi;P. Andreis
Commercial (bovine-porcine) glucagon added in a single dose between 10(-12) and 10(-7) M to neonatal rat hepatocytes in primary cultures with subsequent incubation for 20-24 h, stimulated their entry into the DNA synthesis phase as revealed by [3H]thymidine-labeling and radioautography; about 14 h of incubation was required before an effect was observed. Commercial (bovine) insulin at doses between 10(-11) and 10(-7) M apparently stimulated the entry of hepatocytes into S phase. However, insulin's effect, which needed 20 h for induction, was due to the release of a wave of synchronized hepatocytes from an earlier produced block near the G1/S boundary of their growth-division cycle. Equimolar mixtures of glucagon with insulin from 10(-15)-10(-7) M increased the fraction of hepatocytes synthesizing DNA first at 4-8 h, and then at 20-24 h. Effective doses of glucagon, insulin, and glucagon plus insulin also increased the entry of hepatocytes into mitosis, as found after a 4-h incubation with colchicine (0.1 mM). Withholding inactivated fetal bovine serum from the growth medium for 24 h did not change the mitotic activity either of the untreated or of the glucagon- and glucagon plus insulin-stimulated hepatocytes, but it increased the proliferogenic effect of bovine insulin. Highly purified crystalline (porcine) glucagon, insulin, and glucagon plus insulin also stimulated the growth of hepatocytes in the presence or absence of serum. Finally, equimolar (10(-14) M) mixtures of glucagon with (Bu)2cGMP and of insulin with (Bu)2cAMP increased the hepatocytic replication as efficiently as did glucagon plus insulin at the same dose. The present results show that glucagon and insulin are synergistic, intracycle regulators of the growth of neonatal rat hepatocytes. They also suggest that cyclic necleotides may mediate at least partly the hepatotropic effects of the pancreatic hormones.
