Effects of Insulin, Glucagon, and Insulin/Glucagon Infusions on Liver Morphology and Cell Division After Complete Portacaval Shunt in Dogs

Abstract

Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggest new lines of inquiry about the pathogenesis and/or treatment of several human disease processes.

Glucose and insulin changes following a renoportal shunt in streptozotocin diabetic rats with pancreatic islet isografts under the kidney capsule

“…Such findings are in contrast to the results of insulin infusion experiments using a computer controlled insulin infusion pump that have shown no significant difference between peripheral and intraportal routes of insulin administration in maintaining blood glucose levels following a glucose load [21], or portocaval shunt experiments which show glucose tolerance to be unaltered by such a procedure [22,23]. However a portocaval shunt in dogs does lead to rapid atrophy and other structural abnormalities of the liver, which can be partly prevented by infusion of insulin into the portal vein [24].…”

“…This portal systemic ratio is probably an important aspect of normal glucose metabolism. The systemic delivery of insulin in diabetes via the subcutaneous route or directly into the systemic circulation after a segmental pancreatic graft does not restore normal physiological control of glucose metabolism [24]. Experimental diabetes can be corrected in the rat by transplantation of isolated islets into the liver via the portal vein or into the splenic parenchyma, and in the dog by implantation of dispersed pancreas into the spleen.…”

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo,

“…In this study, this method was used to investigate the consequences of PCS and PCS in conjunction with cyclosporin treatment on hepatic function and basal energy status. The response of the liver to a fructose challenge was monitored by examining the changes in ATP, Pi, and F-1-P levels within the liver as a function of time (28).The dog with a portacaval shunt was chosen as a well-established model for studying hepatic atrophy and contemporaneous hyperplasia (17)(18)(19)(20). The typical injury pattern after PCS consists of a severe reduction in hepatocyte cell size (atrophy) plus organelle disruption and a moderate but persistent stimulation of cell renewal (hyperplasia).…”

“…The typical injury pattern after PCS consists of a severe reduction in hepatocyte cell size (atrophy) plus organelle disruption and a moderate but persistent stimulation of cell renewal (hyperplasia). Insulin and cytosolic extract of the regenerating liver are able to restore the hepatocyte to normal size and to further stimulate hyperplasia (19,20). A disadvantage of earlier studies was that the animals had to be killed, and in vitro assays of the metabolites of interest could be obtained only at selected times.…”

Growth-Stimulating Factor in Regenerating Canine Liver

“…2 Because information about the evolution of these changes within the first 4 days was required to interpret the results of our experiments, control animals had a large side-to-side portacaval shunt with individual ligation of the right and left portal branches, and were killed from ½ to 4 days later (table I). In most of the experiments (tables II and III), a catheter was placed in the ligated left portal branch and led through a subcutaneous tunnel to an infusion pump.…”