Induction of liver cell proliferation in intact rats by amines and glucagon

Administration of isoproterenol followed by glucagon induced DNA synthesis in the liver of intact rats 12-fold over that of non-treated rats. The mixture of heparin, histamine or putrescine, and serotonin followed by glucagon increased DNA synthesis to the same level as in the case of isoproterenol. The stimuli for the induction of liver DNA synthesis appear to be composed of two steps. The first step is stimulated by some catecholamines, the mast-cell components etc., and the second step by glucagon. Each step alone resulted only in a slight increase in DNA synthesis. These results suggest that the substances as mentioned above may be involved in the regulation of liver cell proliferation, and that liver cell proliferation can be induced markedly when both steps of stimuli are provided.