Short-term prednisone use antagonizes insulin's anabolic effect on muscle protein and glucose metabolism in young healthy people
Open accessAbstract
Glucocorticoids cause muscle atrophy and weakness, but the mechanisms for these effects are unclear. The purpose of this study was to test a hypothesis that prednisone (Pred) counteracts insulin's anabolic effects on muscle. A randomized, double-blind cross-over design was used to test the effects of 6 days either Pred (0.8 mg·kg−1·day−1) or placebo use in seven healthy young volunteers. Protein dynamics were measured across the leg using stable isotope tracers of leucine (Leu) and phenylalanine (Phe) after overnight fast and during a hyperinsulinemic (1.5 μU·min−1·kg FFM−1) euglycemic clamp with amino acid replacement. Fasting glucose, amino acids, insulin, and glucagon were higher ( P < 0.01) on Pred vs. placebo, whereas leg blood flow was 18% lower. However, basal whole body and leg kinetics of Leu and Phe were unaltered by Pred. Insulin infusion increased leg glucose uptake in both trials but was 65% lower with Pred than with placebo. Insulin in both trials similarly suppressed whole body flux of Leu and Phe. Importantly, insulin increased net Leu and Phe balance across the leg and the balance between muscle protein synthesis and breakdown, but these changes were 45–140% lower ( P < 0.03) in Pred than in placebo. The present study demonstrates that short-term Pred use in healthy people does not alter whole body or leg muscle protein metabolism during the postaborptive state but causes muscle insulin resistance for both glucose and amino acid metabolism, with a blunted protein anabolism. This interactive effect may lead to muscle atrophy with continued use of glucocorticoids.
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60 mg prednisolone daily stimulated breakdown of skeletal muscle tissue.
“In addition, 60 mg prednisolone daily was shown to stimulate breakdown of skeletal muscle tissue [12].”
From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [12]
The study used prednisone at 0.8 mg/kg/day, not a fixed 60 mg daily dose. Its Discussion (page unavailable) reports that leg protein breakdown rates did not significantly change; prednisone instead blunted insulin’s anabolic effect, which the authors suggest could lead to muscle loss if sustained. (LLM, conf=0.88)
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Regulation of intra-adipose cortisol concentrations in vivo in humans
Hughes, K. A. (2011) · ERA
- Authors
- Short, K. R., Bigelow, M. L., & Nair, K. S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Nair, K. Sreekumaran
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-12
- Volume
- 297
- Issue
- 6
- Pages
- E1260-E1268
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2793048
- OpenAlex
- W2169773860
- Cited by
- 43
- References
- 34
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 2
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (T32-DK-07352, R01DK41973, R01DK041973, T32DK007352)
- National Center for Research Resources (M01-RR00 585, M01RR000585)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- prednisone, glucocorticoids, insulin resistance, muscle protein synthesis, muscle protein degradation, muscle atrophy, glucose metabolism, amino acid metabolism, hyperinsulinemic-euglycemic clamp, leg blood flow, muscle protein balance, postabsorptive state
- MeSH terms
- Adult, Biopsy, Calorimetry, Indirect, Double-Blind Method, Energy Metabolism, Female, Glucocorticoids, Glucose, Humans, Insulin, Insulin Antagonists, Leg, Male, Muscle Proteins, Prednisone, Glucose Clamp Technique, Muscle, Skeletal, Cross-Over Studies
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