Impaired insulin-mediated amino acid plasma disappearance in non-alcoholic fatty liver disease: a feature of insulin resistance.
OBJECTIVE
Insulin resistance is a main feature, and possibly a pathogenic factor, of non-alcoholic fatty liver disease. It is usually measured on glucose metabolism; the effects on amino acid regulation have never been assessed. In particular, no data are available on insulin-dependent branched-chain amino acid metabolism, which is under insulin control.


METHODS
We measured amino acid disappearance from plasma during an euglycemic glucose clamp in 39 biopsy-proven non-alcoholic fatty liver disease patients and in ten control subjects. A primed-constant infusion of insulin (constant rate, 40 mU/m2 per min for 2 h) was used to raise plasma insulin to approximately 100 mU/l. Euglycemia was maintained by a variable glucose infusion, a measure of tissue insulin sensitivity. Plasma amino acids were assayed during the clamp after ninhidrin derivatization.


RESULTS
Fasting plasma amino acids were similar in the two groups. Steady-state insulin levels were significantly higher in non-alcoholic fatty liver disease patients, whereas tissue sensitivity to insulin was reduced by 50%. The plasma disappearance of branched-chain amino acids, as well as the disappearance of the sum of glutamine and glutamate and that of serine were significantly reduced in non-alcoholic fatty liver disease. Differences were maintained after adjustment for steady-state insulin, and correlated with reduced tissue sensitivity to glucose.


CONCLUSIONS
Insulin resistance in non-alcoholic fatty liver disease patients also affects amino acid metabolism, especially for amino acids involved in peripheral muscle nitrogen exchange. The metabolic effects of altered protein/amino acid metabolism must be considered.
Bianchi
G
G
Department of Internal Medicine, Cardioangiology, Hepatology, Università di Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy. giampaolo.bianchi@unibo.it
Marchesini
G
G
Brunetti
N
N
Manicardi
E
E
Montuschi
F
F
Chianese
R
R
Zoli
M
M
D000328:Adult; D000596:Amino Acids / Q000097:blood*; D000597:Amino Acids, Branched-Chain / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D005234:Fatty Liver / Q000097:blood* / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin; D007333:Insulin Resistance; D008297:Male
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D007328:Insulin