Amino acids augment insulin's suppression of whole body proteolysis

• Published in: The American journal of physiology Vol. 257; no. 6 Pt 1; p. E839
• Main Authors: Flakoll, P J, Kulaylat, M, Frexes-Steed, M, Hourani, H, Brown, L L, Hill, J O, Abumrad, N N
• Format: Journal Article
• Language: English
• Published: United States 01-12-1989
• Subjects: 550201 - Biochemistry- Tracer Techniques; Adult; AMINO ACIDS; Amino Acids - blood; Amino Acids - pharmacology; ANIMALS; BASIC BIOLOGICAL SCIENCES; BIOCHEMICAL REACTION KINETICS; BIOLOGICAL FUNCTIONS; CARBON 14 COMPOUNDS; Carbon Radioisotopes; CARBOXYLIC ACIDS; CHEMICAL REACTIONS; DECOMPOSITION; Drug Synergism; FASTING; FUNCTIONS; Glucagon - pharmacology; HORMONES; Humans; INHIBITION; INSULIN; Insulin - pharmacology; ISOTOPE APPLICATIONS; ISOTOPE DILUTION; KINETICS; LABELLED COMPOUNDS; LEUCINE; Leucine - metabolism; Male; MAMMALS; MAN; ORGANIC ACIDS; ORGANIC COMPOUNDS; PEPTIDE HORMONES; PRIMATES; Proteins - metabolism; PROTEOLYSIS; Radioisotope Dilution Technique; REACTION KINETICS; TRACER TECHNIQUES; VERTEBRATES
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1989.257.6.E839

Leucine (LEU) kinetics were assessed using a primed-continuous infusion of L-[1-14C]LEU in normal overnight-fasted male volunteers during a basal period and an experimental period where insulin (INS) was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU.kg-1.min-1 with euglycemia maintained. Two protocols were used: 1) subjects were allowed to develop hypoaminoacidemia or 2) plasma essential amino acids (AA) were maintained near basal levels by frequently monitoring plasma LEU in conjunction with variable infusions of an AA solution (LEU infused = 0.41, 0.72, 0.93, 1.03, 1.31, and 1.35 mumol.kg-1.min-1 at escalating INS doses, respectively). Basal rates of LEU appearance (Ra), nonoxidative disappearance (NORd) and oxidative disappearance (OXRd) were similar in both protocols (means = 1.74, 1.40, and 0.36 mumol.kg-1.min-1, respectively). INS infusions without AA resulted in a progressive decrement in LEU Ra (14 to 45%), NORd (16-41%), and OXRd (3-56%) compared with basal values. The infusion of AA resulted in an additional reduction in endogenous Ra (P less than 0.01; approximately 100% suppression achieved at plasma INS greater than 1,000 microU/ml) and a blunting of NORd reduction (P less than 0.05) at each dose of INS. Observed differences in INS's suppression of LEU Ra between the two protocols suggests the existence of a component of whole body proteolysis that is highly dependent on circulating plasma AA. Therefore, hypoaminoacidemia associated with INS treatment would appear to blunt the responsiveness of INS's suppression of protein breakdown and in the presence of near basal plasma AA, proteolytic suppression by INS is enhanced.