Vacuolar hepatocyte degeneration induced by infusion of 20% glucose solution with insulin after hepatopancreatectomy in rats

To investigate the causes of hepatic dysfunction after extensive resection of the liver together with pancreatectomy, rats were subjected to sham oper ation, to 68% hepatectomy alone, to 90% pancreatectomy alone, or to 68% hep atectomy combined with 90% pancreatectomy (hepatopancreatectomy). Solutions of 5% or 20% glucose were infused post-operatively for 48 h at a constant rate (250 ml/kg body weight/day) under fasting conditions. To improve the s urvival rates of pancreatectomized and hepatopancreatectomized rats given 2 0% glucose, it was necessary to use insulin. In hepatopancreatectomized rat s, infusion of 20% glucose with insulin (1 U/5 g glucose) induced prominent hepatocyte vacuolar degeneration and mitochondrial swelling, associated wi th reduced hepatic protein content. The severity of histological changes wa s proportional to the insulin dose and the activity of hepatic glucokinase, a key glycolytic enzyme. These histological changes were observed in pancr eatectomized rats albeit in a milder form, but not in sham-operated or hepa tectomized rats given 20% glucose nor in any rats given 5% glucose. Our res ults suggest that hepatopancreatectomy followed post-operatively by a high glucose load and exogenously administered insulin enhances the development of hepatocyte swelling.