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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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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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