inhibition of liver regeneration by somatostatin infusion and its reversal by pancreatic polypeptide and hepatocyte-stimulating substance

ABSTRACT

Several hepatotrophic hormones are known to be involved in initiating and potentiating the hepatic proliferative response to injury or hepatectomy. Little is known, however, about factors promoting termination of the regenerative response when the liver is restored. Because somatostatin [SRIF], isolated from gastric pancreatic and portal circulation, is an inhibitory hormone, we attempted to evaluate is potential role in regulating liver cell regeneration. We also studied the relationship of SRIF to insulin, glucagon, pancreatic polypeptide, and hepatocyte-stimulating substance on regenerating the liver following extended hepatectomy in rats. Male Sprague-Dawley rats were either sham-operated [n = 6] or subjected to 68% hepatectomy [n = 35]. Subcutaneous infusions of either saline or hormones were started 18-24 h preoperatively and continued until sacrifice 24 h following hepatectomy. At sacrifice, peripheral blood was obtained to determine serum insulin, glucagon, and SRIF levels. Liver regeneration was assayed by measuring the incorporation of radiolabelled thymidine into hepatocyte DNA. Liver regeneration was significantly [P<0.01] inhibited by SRiF Glucagon or glucagon and insulin combined did not reverse this effect. Insulin and glucagon levels were not significantly influenced by SRIF infusion. Pancreatic polypeptide and hepatocyte stimulating substance were both able to reverse the inhibitory effect of SRIF on liver regeneration and at the same time caused serum glucagon levels to increase and serum insulin levels to decrease. Thus SRIF inhibits liver regeneration after hepatectomy either by acting directly on the hepatocytes or via other factors which are not insulin and glucagon. Pancreatic polypeptide and hepatocyte stimulating substance reverse SRIF mediated inhibition of liver regeneration, possibly by changing insulin and glucagon levels, although other mechanisms may be involved