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Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range.
Open accessAbstract
Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
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“Because GCs are known to promote the catabolism of proteins, including serum albumin (, ), there is a risk that GA levels will be influenced by GC excess.”
From Glucose Metabolism Abnormalities in Cushing Syndrome: From Molecular Basis to Clinical Management (2017) · cites this paper as [242]
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Glucocorticoids abate p70S6kand eIF4E function in L6 skeletal myoblasts
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Effects of epinephrine infusion on leucine and alanine kinetics in humans
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Background3 The use of stable isotopes in metabolic investigation
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“…by a single bout of resistance exercise may be potentiated by high circulating levels of insulin (Fluckey et al. 1996; Roy et al. 1997; Biolo et al. 1999) or growth hormone (Fryburg and Barrett 1993), or may be inhibited by high levels of glucocorticoids (Simmons et al. 1984; Louard et al. 1994).”
BackgroundResistance Training in Post-Metabolic and Bariatric Surgery Patients: A Systematic Review
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“Cortisol is known to be a counter regulatory hormone during prolonged hypoglycemia and stimulates gluconeogenesis by increasing the delivery of gluconeogenic substrates via lipolysis and proteolysis, and by enhancing the activity of key gluconeogenic enzymes [26-31].”
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Glucocorticoids antagonize insulin's antiproteolytic action on skeletal muscle in humans
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“…homeostasis during the session (e.g., reduced T clearance rates (Ahtiainen et al. 2015)) and/or the level of substrate breakdown/consumption (Simmons et al. 1984; Yarasheski et al. 1992) and thus indicates a stress dose-response association, and (5) acute hormonal responses to a nonchanging…”
BackgroundInfluentialEffect of immunocastration and housing conditions on pig carcass and meat quality traits1
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“The observation in the current study that DEX did not affect the basal phosphorylation of PHAS-I or p70 may in part explain the failure of previous investigations to detect an effect of glucocorticoids on protein synthesis in vivo (1, 5, 11, 17, 26).”
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Metadata
- Authors
- Simmons, P. S., Miles, J. M., Gerich, J. E., & Haymond, M. W.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Haymond, M W
- Venue
- Journal of Clinical Investigation
- Published
- 1984-02-01
- Volume
- 73
- Issue
- 2
- Pages
- 412-420
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC425032
- OpenAlex
- W2075956591
- Cited by
- 286
- References
- 41
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 13 · 2020: 15 · 2019: 6 · 2018: 6 · 2017: 14 · 2016: 2 · 2015: 6 · 2014: 10 · 2013: 11 · 2012: 3
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wasie Foundation
- Mayo Foundation for Medical Education and Research
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- plasma cortisol, proteolysis, leucine kinetics, alanine synthesis, amino acid metabolism, protein metabolism, muscle atrophy, insulin, glucagon, C-peptide, nitrogen balance, muscle protein turnover, nitrogen retention, nitrogen excretion, nitrogen intake
- MeSH terms
- Adult, Alanine, Amino Acids, Blood Glucose, Humans, Hydrocortisone, Kinetics, Leucine, Nitrogen, Peptide Hydrolases
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