The DOI matches its Crossref record; 46 of the 47 references it cites were found in a registry or an index.
Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia
Open accessAbstract
Background Reduced postprandial muscle proteolysis is mainly due to increased insulin availability. Whether rates of proteolysis in response to low physiologic doses of insulin are affected by aging is unknown. Objectives We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt-protein kinase B (PKB). Design Groups of 8 young [mean (+/-SD) age: 24.5 +/- 1.8 y] and older (65.0 +/- 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine approximately 120 micromol/L) clamp procedures at plasma insulin concentrations of approximately 5 and approximately 15 microIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with D(5)-phenylalanine and [1,2-(13)C(2)]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures. Results Basal LPB rates were not different between groups (66 +/- 11 compared with 51 +/- 10 nmol leucine x 100 mL leg(-1) x min(-1) and 30 +/- 5 compared with 24 +/- 4 nmol phenylalanine x 100 mL leg(-1) x min(-1) in young and older groups, respectively). However, although insulin at approximately 15 microIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins. Conclusions At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“With aging, the normal balance between muscle protein synthesis and degradation is shifted toward net catabolism, the body's anabolic response to dietary protein or amino acids is limited, 46,120,122,123 and the normal antiproteolytic response to insulin is impaired.46,124,125”
From Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group (2013) · cites this paper as [124]
Citations
Cites
Epidemiology of Sarcopenia among the Elderly in New Mexico
Baumgartner, R. N., Koehler, K. M., Gallagher, D., Romero, L., Heymsfield, S. B., Ross, R. R., Garry, P. J., & Lindeman, R. D. (1998) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009520 · Cited by 4,004
Katz, A., Nambi, S. S., Mather, K., Baron, A. D., Follmann, D. A., Sullivan, G., & Quon, M. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.7.6661 · Cited by 3,931 · cited 2×
“tivity check index (QUICKI) (33) (young group, 0.”
InfluentialStitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00211-4 · Cited by 1,964
Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle
Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., Wackerhage, H., Taylor, P. M., & Rennie, M. J. (2005) · The FASEB Journal · doi:10.1096/fj.04-2640fje · Cited by 1,211
Self-citationAppendicular skeletal muscle mass: effects of age, gender, and ethnicity
Gallagher, D., Visser, M., De Meersman, R. E., Sepúlveda, D., Baumgartner, R. N., Pierson, R. N., Harris, T., & Heymsfield, S. B. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.83.1.229 · Cited by 966
Katsanos, C. S., Kobayashi, H., Sheffield-Moore, M., Aarsland, A., & Wolfe, R. R. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00488.2005 · Cited by 923
Ceramide Content Is Increased in Skeletal Muscle From Obese Insulin-Resistant Humans
Adams, J. M., Pratipanawatr, T., Berria, R., Wang, E. L., DeFronzo, R. A., Sullards, M. C., & Mandarino, L. J. (2004) · Diabetes · doi:10.2337/diabetes.53.1.25 · Cited by 677
Abumrad, N. N., Rabin, D. D., Diamond, M. P., & LACY, W. W. (1981) · Metabolism · doi:10.1016/0026-0495(81)90074-3 · Cited by 569
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
Greenhaff, P. L., Karagounis, L. G., Peirce, N., Simpson, E. J., Hazell, M., Layfield, R., Wackerhage, H., Smith, K., Atherton, P., Selby, A., et al. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90411.2008 · Cited by 495
Self-citation
Cited by
Sorted by citations
Bauer, J., Biolo, G., Cederholm, T., Cesari, M., Cruz-Jentoft, A. J., Morley, J. E., Phillips, S., Sieber, C., Stehle, P., Teta, D., et al. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.021 · Cited by 2,553
Acute skeletal muscle wasting in critical illness
Puthucheary, Z. A., Rawal, J., McPhail, M., Connolly, B., Ratnayake, G., Chan, P., Hopkinson, N. S., Padhke, R., Dew, T., Sidhu, P. S., et al. (2013) · JAMA · doi:10.1001/jama.2013.278481 · Cited by 2,103
Self-citationMitchell, W. K., Williams, J., Atherton, P., Larvin, M., Lund, J., & Narici, M. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00260 · Cited by 1,377
Self-citationWilkinson, D. J., Piasecki, M., & Atherton, P. J. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.07.005 · Cited by 950
Self-citationSarcopenia: characteristics, mechanisms and functional significance
Narici, M. V., & Maffulli, N. (2010) · British Medical Bulletin · doi:10.1093/bmb/ldq008 · Cited by 827
Metadata
- Authors
- Wilkes, E. A., Selby, A. L., Atherton, P. J., Patel, R., Rankin, D., Smith, K., & Rennie, M. J.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Rennie, Michael J
- Venue
- The American Journal of Clinical Nutrition
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 90
- Issue
- 5
- Pages
- 1343-1350
- ISSN
- 0002-9165 (ISSN-L)
- OpenAlex
- W2118035665
- Cited by
- 204
- References
- 47
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 4 · 2023: 11 · 2022: 10 · 2021: 14 · 2020: 17 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 17 · 2015: 11 · 2014: 13 · 2013: 18 · 2012: 18
- FWCI
- 6.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/X5106971, BB/C516779/1)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- insulin resistance, muscle protein degradation, aging, sarcopenia, Akt/protein kinase B, mTOR signaling, muscle protein synthesis, older adults
- MeSH terms
- Adult, Aged, Aging, Amino Acids, Female, Humans, Insulin, Leg, Leucine, Male, Muscle Proteins, Muscular Diseases, Proteins, Glucose Clamp Technique, Proto-Oncogene Proteins c-akt
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
