Glucose and potassium metabolic responses to insulin during liver transplantation.

Insulin regulates glucose and potassium metabolism by acting differently upon peripheral tissues (e.g., skeletal muscle) and the splanchnic bed, including the liver. Liver disease is accompanied by "insulin resistance" of glucose metabolism, whereby glucose intolerance occurs despite relatively increased plasma insulin concentration. However, it is unknown whether insulin resistance extends to potassium metabolism. Further, it is uncertain whether the hyperglycemia and alterations of plasma potassium concentration observed during liver transplantation result from changes in circulating insulin concentration, altered sensitivity to insulin, or both, as the diseased liver is removed and replaced with a graft organ. The present study evaluated the role of the liver in maximal insulin responsiveness of whole-body glucose and potassium metabolism, using a hyperinsulinemic clamp technique, to identify the mechanism(s) underlying post-reperfusion hyperglycemia and intraoperative hyperkalemia. Two protocols were employed: in protocol 1 (n = 10), no exogenous insulin was administered. In protocol 2 (n = 10), an intravenous insulin bolus (666 mU . kg-1) was administered after anesthesia induction, followed by an infusion at 500 mU.m-2.min-1, which continued until 3 hours after portal vein unclamping. Plasma concentrations of glucose and potassium were regulated by glucose and potassium chloride infusion (euglycemic eukalemic clamp). Insulin-stimulated exogenous glucose and potassium uptakes were determined in protocol 2 before skin incision and during the dissection, anhepatic, and neohepatic stages. In both protocols, serial measurements of hemodynamic arterial blood gases, glucose, free fatty acids, potassium, insulin, and glucagon concentrations were made. Without insulin (protocol 1), progressive hyperglycemia peaked after portal vein unclamping (post-reperfusion hyperglycemia), with no concomitant decrease in plasma insulin concentration. Intraoperative plasma potassium concentration did not change. Insulin infusion (protocol 2) produced a stable hyperinsulinemia (approximately 2000 microU/mL). Hyperinsulinemia did not eliminate post-reperfusion hyperglycemia. Insulin-stimulated glucose uptake, in mg . kg-1 . min-1, was 8.10 +/- 0.78 (mean +/- SE) before skin incision, 7.62 +/- 0.82 during the hepatic dissection, 4.40 +/- 0.75 during the anhepatic stage, and 4.06 +/- 0.74 at 3 hours after portal vein unclamping. Insulin-stimulated potassium uptake, in mEq . kg-1 . hr-1, was 0.24 +/- 0.02 before skin incision, 0.21 +/- 0.04 during hepatic dissection, 0.07 +/- 0.02 during the anhepatic stage, and 0.21 +/- 0.04 and 0.19 +/- 0.05 at 30 minutes and 3 hours, respectively, after portal vein unclamping. We conclude that post-reperfusion hyperglycemia is not due to inadequate insulin stimulation. Liver disease-induced insulin resistance of glucose metabolism is exacerbated by hepatectomy and is not reversed during the intraoperative neohepatic stage. Liver disease does not impair maximal insulin-stimulated potassium uptake. The liver, even with end-stage disease, accounts for approximately 70% of insulin-stimulated potassium uptake.