MECHANISMS OF HYPERINSULINEMIA AND HYPERGLUCAGONEMIA AFTER LIVER-TRANSPLANTATION

These studies were undertaken to evaluate the mechanisms for changes i n plasma insulin and glucagon levels observed post-liver transplantati on. Two groups of pigs were studied: a control group (n = 8) underwent ; laparotomy and catheter placement in the carotid artery and portal a nd hepatic veins. Hepatic blood flow was measured by ultrasonic flow p robes placed around the hepatic artery and portal vein. An experimenta l group (n = 8) underwent orthotopic liver transplantation and similar instrumentation, On Day 1 after surgery, an estimate of insulin and g lucagon secretion and hepatic extraction was determined using arteriov enous difference techniques, Serum assays were performed for markers o f hepatic and renal function. Plasma insulin levels of the transplante d pigs were higher in the carotid artery (4 +/- 1 mu U/m(2) vs 7 +/- 1 mu U/ml), but not in the hepatic vein (5 +/- 1 mu U/ml vs 7 +/- 1 mu U/ml) and in the portal vein (10 +/- 2 mu U/ml vs 12 +/- 2 mu U/ml). A rterial plasma C-peptide was significantly greater in the transplanted group (0.23 +/- 0.02 ng/ml vs 0.42 +/- 0.03 ng/ml); however, the mola r ratio of C-peptide and insulin was not different between the two gro ups (3.6 +/- 0.9 vs 3.4 +/- 0.4), Plasma glucagon levels of the transp lanted pigs were significantly elevated in the carotid artery (111 +/- 11 pg/ml vs 323 +/- 65 pg/ml), portal Vein (221 +/- 27 pg/ml vs 495 /- 69 pg/ml), and hepatic vein (142 +/- 15 pg/ml vs 395 +/- 58 pg/ml). The estimate of pancreatic secretion of insulin (115 +/- 25 mu U/kg.m in) vs 71 +/- 21 mu U/kg.min) and glucagon (2.0 +/- 0.4 ng/kg min vs 2 .7 +/- 0.7 ng/kg.min) and the fractional hepatic extraction rate of in sulin (35 +/- 8% vs 32 +/- 5%) were not different between the two grou ps, However, the hepatic fractional extraction rate of glucagon was si gnificantly decreased in the transplanted group (25 +/- 5% vs 11 +/- 3 %), Therefore, the hyperglucagonemia observed 24 hr following liver tr ansplantation is partly due to reduced hepatic fractional extraction o f glucagon while the hyperinsulinemia is mainly due to the nonhepatic clearance of insulin. We speculate that decreased renal function may c ontribute to the hyperinsulinemia, elevated C-peptide concentrations, and hyperglucagonemia. (C) 1997 Academic Press.