Glucose and lipid metabolism after liver transplantation in inbred rats: consequences of hepatic denervation.
The liver plays a central role in glucose and lipid homeostasis. Because liver transplantation severs the hepatic nerves which influence this function, we hypothesized that insulin resistance and hyperlipidemia develop after liver transplantation, thus increasing the atherosclerotic risk. Therefore, we studied inbred rats 8 months after orthotopic liver transplantation (Tx, n = 39) or laparotomy (sham, n = 37) by either oral glucose tolerance test (Tx, n = 13; sham, n = 8), meal tolerance test (Tx, n = 9; sham, n = 13), or euglycemic hyperinsulinemic clamp with tritiated glucose infusion (Tx, n = 17; sham, n = 16). We found that liver transplantation significantly increased basal hepatic glucose production (HGP) in the clamp study by 20% (37.3 +/- 2.2 vs 31.0 +/- 2.1 micromol kg -1 .min -1 , P < .05) and fasting plasma low-density lipoprotein (LDL) cholesterol by 36% (0.79 +/- 0.06 vs 0.58 +/- 0.05 mmol/L, P < .05). However, it did not affect HGP, total glucose uptake, metabolic clearance rate of insulin, and suppression of plasma nonesterified fatty acids, which were all normal in response to rising plasma insulin concentrations in the dose-response clamp studies. The oral glucose tolerance test and meal tolerance test also showed normal glucose and nonesterified fatty acids homeostasis with adequate pancreatic insulin secretion and hepatic insulin clearance after liver transplantation. The only consequences of liver transplantation are increased basal HGP and plasma LDL cholesterol, which may be caused by persistent vagal denervation of the liver. Although insulin resistance is absent, elevated plasma LDL cholesterol increases the atherosclerotic risk.
Kissler
Hermann J
HJ
Division of Experimental Surgery and Endocrine Research Laboratory, Friedrich Alexander University, Erlangen, Germany. h-kissler@northwestern.edu
Hauffen
Jürgen
J
Hennig
René
R
Gepp
Heike
H
Schwille
Paul O
PO
D000818:Animals; D001835:Body Weight; D003714:Denervation; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000294:innervation*; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D005947:Glucose