The Role of Intraperitoneal Insulin on Liver Regeneration in Rat

ABSTRACT

Insulin is well known to have a hepatotrophic effect, but exogenous insulin has a negative effect on liver regeneration because it decreases the level of endogenous insulin. Howerver intraportal exogenous insulin will have some differences. This study was set up to analyse the effect of portal insulin via intraperitoneal route on liver regeneration in rats which have a normal pancreas with or without liver cirrhosis after partial hepatectomy. Beforehand, insulin levels of the portal blood at the time intervals of 0, 30, 60, 120, and 240 minutes after intraperitoneal injection of insulin were measured and compared with those after subcutaneous injection. The results were: 1.5, 140.9, 58.6, 20.4, 14.3 g/ml in intraperitoneal group(n=14) and 1.5, 22.3, 27.1, 32.4, 29.1 g/ml in subcutaneous group(n=14). Intraperitoneally injected insulin was absorbed more rapidly than subcutaneously injected insulin. Thirty nine rats with normal liver were divided into 5 groups A(n=8): intraperitoneal saline, B(n=9): intraperitoneal insulin 2 IU/Kg, C(n=7): subcutaneuos insulin 2 IU/Kg, D(n=7): intraperitoneal insulin 5 IU/Kg, E(n=8): subcutaneous insulin 5 IU/Kg. They were all 2/3 partial hepatectomized and remnant livers were obtained after 24 hours after hepatectomy. Ninety minutes before sacrifice, 100 Ci,H3-thymidine was injected intraperitoneally and their C.P.M./ g of DNA was measured and compared with each other groups. The same procedures were done with another twenty seven rats with liver cirrhosis (A'(n=5), B'(n=6), C'(n=6), D'(n=5), E'(n=5)) which was induced by oral ingestion of CCl4 for 12 weeks. The results were: 38.29, 25.77, 14.37, 34.04, 23.83 C.P.M./ g in normal rat group and 23.76, 8.11, 10.89, 8.80, 12.22 C.P.M./ g. In normal rat, the C.P.M.'s of intraperitoneal groups were higher than those of subcutaneous group and the difference was statistically significant between A and C group (p<0.05). In cirrhotic group, there were not any significant differences between any two groups. It can be concluded that exogenous insulin has an inhibitory effect on liver regeneration. But intraperitoneal insulin exerts less inhibitory effect on liver regeneration than subcutaneous insulin because intraportal insulin is more potent in liver regeneration and has less negative feed back on endogenous insulin than systemic insulin.