Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting.
This study examines the independent effects of insulin and amino acids on protein metabolism after a 12-h and 4-day fast in healthy volunteers. Leucine (Leu) kinetics were examined during sequential insulin infusions of 0 (group I) or 0.0125 (groups II and III), 1.2, and 10 mU.kg-1.min-1. Plasma Leu was maintained at 12-h fasted levels in groups I and II and at 84-h fasted levels in group III. Four-day fast (vs. 1 day, P less than 0.01) was associated with a 79% drop in plasma insulin and elevations in plasma Leu (122%), Leu rates of appearance (Ra) (21%), and Leu oxidation (56%), and no change in nonoxidative rates of disappearance (Rd). Insulin resulted in a dose-dependent suppression of endogenous Leu Ra with group III = I greater than II. Leu oxidation rose 1.7-fold in group III at the highest insulin dose but remained stable in the two other groups. In conclusion, 4-day fasting is associated with enhanced proteolysis and Leu oxidation with no change in nonoxidative Rd (protein synthesis). Elevated branched-chain (and other) amino acids were required to restore tissue sensitivity and specificity to the effects of insulin on protein metabolism after 4 days of fasting.
Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
M
M
Frexes-Steed
M L
ML
Warner
N
N
Bulus
P
P
Flakoll
N N
NN
Abumrad
D000328:Adult; D000596:Amino Acids / Q000097:blood; D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D004837:Epinephrine / Q000097:blood; D005215:Fasting; D005934:Glucagon / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000502:physiology*; D007930:Leucine / Q000378:metabolism; D008297:Male
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D007930:Leucine; D006854:Hydrocortisone; D004837:Epinephrine