Hyperammonemia induced by administration of glucose and insulin after hepatopancreatectomy in rats

Massive resection of both the liver and pancreas is performed as a radical procedure in some cases of advanced biliary cancer, but it has been reported that this disease is frequently complicated by hyperbilirubinemia or hepatic insufficiency postoperatively, which is a serious hindrance to performing such extended surgery (Nimura et al., 1991; Nakamura et al., 1992). To investigate the pathogenesis of hepatic dysfunction after hepatopancreatectomy, we performed 4 surgical procedures consisting of 68% hepatectomy, 90% pancreatectomy, 68% hepatectomy plus 90% pancreatectomy (hepatopancreatectomy) and sham-surgery in rats. Then, rats were continuously infused with 5% or 20% glucose solution at a constant speed (50 mL/day) for 24 hours in the fasting state, thus creating a total of 8 groups. During infusion of 20% glucose solution into rats with pancreatectomy or hepatopancreatectomy, insulin (1 U/5 g glucose) was added to the solution to adjust the blood glucose. In rats infused with 20% glucose solution with added insulin after hepatopancreatectomy, the blood glucose level did not differ, but adenosine 5'-triphosphate (ATP) and energy charge levels in the liver tissue were significantly lower, while the blood ammonia level was significantly higher than those in the other 7 groups. These results demonstrate that continuous infusion of high concentrations of glucose solution with added insulin after hepatopancreatectomy in rats reduces hepatic mitochondrial function, resulting in hyperammonemia due to reduced urea synthesis.