The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle
Open accessAbstract
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 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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Cites
Protein turnover in mammalian tissues and in the whole body
Waterlow, J. C., Garlick, P. J., & Millward, D. J. (1978) · Medical Entomology and Zoology · Cited by 1,227
Role of amino acid transport and countertransport in nutrition and metabolism.
Christensen, H. N. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.1.43 · Cited by 1,105
Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm.
Fulks, R. M., Li, J. B., & Goldberg, A. L. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42013-9 · Cited by 914
Intracellular free amino acid concentration in human muscle tissue.
Bergström, J., Fürst, P., Norée, L. O., & Vinnars, E. (1974) · Journal of Applied Physiology · doi:10.1152/jappl.1974.36.6.693 · Cited by 730
Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.
Gelfand, R. A., & Barrett, E. J. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113033 · Cited by 522
The regulation of amino acid transport in animal cells
Guidotti, G., Borghetti, A. F., & Gazzola, G. C. (1978) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(78)90009-6 · Cited by 467
The regulation of neutral amino acid transport in mammalian cells
Shotwell, M. A., Kilberg, M. S., & Oxender, D. L. (1983) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(83)90003-5 · Cited by 458
Radioactive and Stable Isotope Tracers in Biomedicine
Bramlet, R. C. (1993) · Clinical Nuclear Medicine · doi:10.1097/00003072-199305000-00027 · Cited by 393
Leg Blood Flow during Exercise in Man
Jorfeldt, L., & Wahren, J. (1971) · Clinical Science · doi:10.1042/cs0410459 · Cited by 353
Transmembrane transport and intracellular kinetics of amino acids in human skeletal muscle
Biolo, G., Fleming, R. Y., Maggi, S. P., & Wolfe, R. R. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.268.1.e75 · Cited by 287
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Research works printed but not linked: 2
- Kimbal, S. R., K. E. Flaim, D. E. Peavy, and L. S. Jefferson. 1989. Protein metabolism. In Diabetes Mellitus, Theory and Practice. M. Ellemberg, and M. Rifkin, editors. Elsevier Science Publishing Co., Inc., New York/Amsterdam/ London. 41-50.
- Miller, L. L. 1962. The role of the liver and the non-hepatic tissues in the regulation of free amino acid levels in the blood. In Amino Acid Pools. J. T. Holden, editor. Elsevier Science Publishers B. V., Amsterdam. 708-722.
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Metadata
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › 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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