Post-absorptive and insulin-mediated muscle protein metabolism in liver-transplanted patients.
Cirrhotic patients after liver transplantation show a near-normal glucose homeostasis when in stable condition. In contrast, the basal and insulin-mediated whole-body protein metabolism remain altered several years after the graft. To examine whether the persisting defect of protein metabolism was due to the muscle, 7 non-diabetic liver-transplanted patients in stable condition were studied by means of the catheterization of the brachial artery and the deep forearm vein (to measure the balance across the forearm) and the infusion of labelled leucine and phenylalanine associated with indirect calorimetry. Whole-body proteolysis (as determined by endogenous leucine flux, ELF), protein synthesis (from non-oxidative leucine disposal, NOLD) and leucine oxidation (LO) were reduced in comparison to previously obtained values in a normal population. Insulin infusion (while maintaining euglycemia) induced a not significant variation of forearm phenylalanine Ra (24.4-->16.5 micromol/100 ml forearm min(-1); proteolysis) and Rd (18.5-->19.7; protein synthesis). In contrast, the whole-body insulin-dependent inhibitions of ELF (31.5-->21.8 micromol/m(2) min) and NOLD (27.3-->18.4) were impaired with respect to a normal population. On the basis of the present results, we conclude that skeletal muscle is not responsible for the alterations of leucine metabolism persisting after liver transplantation. By exclusion, this points to the liver as the major determinant of the leucine metabolism defect.
Luzi
L
L
Division of Medicine, San Raffaele Scientific Institute, University of Milan, Via Olgettina 60, I-20132 Milan, Italy.
Regalia
E
E
Pulvirenti
A
A
Piceni Sereni
L
L
Spessot
M
M
Romito
R
R
Baratti
D
D
Terruzzi
I
I
Mazzaferro
V
V
D005542:Forearm; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000601:surgery; D016031:Liver Transplantation; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D010447:Peptide Hydrolases / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D019518:Postprandial Period
D007328:Insulin; D009124:Muscle Proteins; D010649:Phenylalanine; D010447:Peptide Hydrolases; D007930:Leucine