Hepatic regeneration in the absence of portal viscera.

In an effort to investigate the influence of portal factors on hepatic regeneration in the rat and to clarify glucagon's apparent regulatory role, a rat preparation was developed which was totally devoid of portal viscera and thus deficient in all possible hepatotrophic substances of portal origin. It was found that, following partial hepatectomy, such an eviscerate rat was able to undergo hepatic deoxyribonucleic acid (DNA) synthesis, but the peak DNA synthetic response was significantly delayed by such portal deprivation. As demonstrated by a group of rats with intact portal viscera, but with a portacaval shunt, reduction of blood supply to the hepatic remnant by diversion of portal flow accounted for only a portion of the delay. The remainder of the delay encountered in the eviscerate group was attributed to the deprivation of specific portal substances. Since glucagon supplementation administered to the deficient eviscerate animal restored peak DNA synthesis to the time of its appropriate shunted control, this hepatotrophic substance is a major portal factor modifying the response to partial hepatectomy. Evidence is cited which suggests that glucagon's influence on DNA synthesis is mediated through the formation of cyclic adenosine monophosphate (AMP) and subsequent histone phosphorylation.