Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle
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We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers, using stable isotopic tracers of amino acids. Calculations of muscle protein synthesis, breakdown, and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy. Insulin was infused (0.15 mU/min per 100 ml leg) into the femoral artery to increase femoral venous insulin concentration (from 10 +/- 2 to 77 +/- 9 microU/ml) with minimal systemic perturbations. Tissue concentrations of free essential amino acids decreased (P < 0.05) after insulin. The fractional synthesis rate of muscle protein (precursor-product approach) increased (P < 0.01) after insulin from 0.0401 +/- 0.0072 to 0.0677 +/- 0.0101%/h. Consistent with this observation, rates of utilization for protein synthesis of intracellular phenylalanine and lysine (arteriovenous balance approach) also increased from 40 +/- 8 to 59 +/- 8 (P < 0.05) and from 219 +/- 21 to 298 +/- 37 (P < 0.08) nmol/min per 100 ml leg, respectively. Release from protein breakdown of phenylalanine, leucine, and lysine was not significantly modified by insulin. Local hyperinsulinemia increased (P < 0.05) the rates of inward transport of leucine, lysine, and alanine, from 164 +/- 22 to 200 +/- 25, from 126 +/- 11 to 221 +/- 30, and from 403 +/- 64 to 595 +/- 106 nmol/min per 100 ml leg, respectively. Transport of phenylalanine did not change significantly. We conclude that insulin promoted muscle anabolism, primarily by stimulating protein synthesis independently of any effect on transmembrane transport.
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Prolonged periods where MPS exceeds muscle protein breakdown result in net muscle protein accretion, and periods where muscle protein breakdown exceeds MPS result in loss of muscle mass, with changes in MPS thought to be most consequential.
“Prolonged periods where MPS exceeds muscle protein breakdown will result in the net muscle protein accretion, and periods where muscle protein breakdown exceeds MPS will result in the loss of muscle mass, with changes in MPS thought to be most consequential [49].”
From Nutritional Considerations for the Vegan Athlete (2023) · cites this paper as [49]
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- Authors
- Biolo, G., Declan Fleming, R. Y., & Wolfe, R. R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Shriners Hospitals for Children - Galveston (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1995-02-01
- Volume
- 95
- Issue
- 2
- Pages
- 811-819
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC295560
- OpenAlex
- W2041707781
- Cited by
- 442
- References
- 46
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 24 · 2021: 16 · 2020: 7 · 2019: 10 · 2018: 4 · 2017: 11 · 2016: 18 · 2015: 11 · 2014: 13 · 2013: 11 · 2012: 13
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- Funders
- University of Texas Medical Branch
- Shriners Hospitals for Children
- National Institutes of Health (5r01dk033952-14)
- U.S. Public Health Service (00074)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 33952, DK-38010, R01DK038010)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- insulin, hyperinsulinemia, skeletal muscle, muscle protein synthesis, muscle protein degradation, amino acid transport, muscle anabolism, essential amino acids, phenylalanine, leucine, lysine, alanine
- MeSH terms
- Adult, Alanine, Amino Acids, Biological Transport, Femoral Vein, Humans, Hyperinsulinism, Insulin, Kinetics, Leucine, Lysine, Male, Mathematics, Models, Biological, Phenylalanine, Reference Values, Protein Biosynthesis, Muscle, Skeletal
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