Implications of host pancreatic hormones in the restart of grafted liver

Abstract

Regulatory roles of insulin and glucagon in hepatic metabolism and function are well described. However, little is known about implications of host pancreatic hormones in primary function of grafted liver. This study aimed to investigate it in relation to hepatic mitochondrial function. Insulin, c-peptide, and glucagon in peripheral blood were monitored for 2 days in clinical liver transplantation by a continuous sampling technique to avoid influences of hormonal oscillation. In grafts with immediate function (n = 10), smooth increase of arterial ketone body ratio reflecting hepatic intramitochondrial redox state was accompanied by increased c-peptide and decreased glucagon, resulting in the increase of c-peptide/glucagon ratio. In other functioning grafts (n = 20), where ketone body ratio was rather lower, increased glucagon level, observed also during anhepatic phase, resulted in the slower increase of c-peptide/glucagon ratio. These were accompanied by increased free fatty acid and ketone body levels. In primary nonfunction (n = 4), rapid increase of c-peptide accompanied by hyperglycemia resulted in the accelerated increase of c-peptide/glucagon ratio, but ketone body ratio did not show any increase. Insulin/c-peptide ratio also showed a rapid increase. These findings suggest that the increase of insulin/glucagon ratio in portal blood, potentially influenced by recipient condition, is associated with the recovery of mitochondrial energy metabolism in survived hepatic grafts. However, this relationship does not work in failed grafts, where irreversible impairment of energy metabolism is attributed to graft itself.