Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man

Journal Article · Wed Jul 01 04:00:00 EDT 1987 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI113033· OSTI ID:6025726

Gelfand, R A; Barrett, E J

Although insulin stimulates protein synthesis and inhibits protein breakdown in skeletal muscle in vitro, the actual contribution of these actions to its anabolic effects in man remains unknown. Using the forearm perfusion method together with systemic infusion of L-(ring-2,6-3H)phenylalanine and L-(1-/sup 14/C)leucine, we measured steady state amino acid exchange kinetics across muscle in seven normal males before and in response to a 2-h intraarterial infusion of insulin. Postabsorptively, the muscle disposal (Rd) of phenylalanine (43 +/- 5 nmol/min per 100 ml forearm) and leucine (113 +/- 13) was exceeded by the concomitant muscle production (Ra) of these amino acids (57 +/- 5 and 126 +/- 9 nmol/min per dl, respectively), resulting in their net release from the forearm (-14 +/- 4 and -13 +/- 5 nmol/min per dl, respectively). In response to forearm hyperinsulinemia (124 +/- 11 microU/ml), the net balance of phenylalanine and leucine became positive (9 +/- 3 and 61 +/- 8 nmol/min per dl, respectively (P less than 0.005 vs. basal). Despite the marked increase in net balance, the tissue Rd for both phenylalanine (42 +/- 2) and leucine (124 +/- 9) was unchanged from baseline, while Ra was markedly suppressed (to 33 +/- 5 and 63 +/- 9 nmol/min per dl, respectively, P less than 0.01). Since phenylalanine is not metabolized in muscle (i.e., its only fates are incorporation into or release from protein) these results strongly suggest that in normal man, physiologic elevations in insulin promote net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis.

• Research Organization: Yale Univ. School of Medicine, New Haven, CT
• OSTI ID: 6025726
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 80:1; ISSN JCINA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANABOLISM
ANIMAL TISSUES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
DISEASES
HORMONES
INSULIN
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUCINE
MAMMALS
MAN
METABOLIC DISEASES
METABOLISM
MUSCLES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PATHOGENESIS
PEPTIDE HORMONES
PERFUSED TISSUES
PHENYLALANINE
PRIMATES
PROTEINS
REACTION KINETICS
SYNTHESIS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES