Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism

Fujita, S.; Glynn, E. L.; Timmerman, K. L.; Rasmussen, B. B.; Volpi, E.

doi:10.1007/s00125-009-1430-8

Cited by 164Muscle metabolism and nutritionNutrition and Health in AgingMetabolism, Diabetes, and Cancer

Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism

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Fujita, S., Glynn, E. L., Timmerman, K. L., Rasmussen, B. B., Volpi, E.·2009·Diabetologia

DOI 10.1007/s00125-009-1430-8PMC PMC2843438

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Abstract

Aims/hypothesis The physiological increase in muscle protein anabolism induced by insulin is blunted in healthy, glucose-tolerant older adults. We hypothesised that the age-related defect in muscle protein anabolism is a true insulin resistance state and can be overridden by supraphysiological hyperinsulinaemia.Methods We used dye dilution, stable isotopic and immunoblotting techniques to measure leg blood flow, muscle protein synthesis, protein kinase B/mammalian target of rapamycin (Akt/mTOR) signalling, and amino acid kinetics in 14 healthy, glucose-tolerant older volunteers at baseline, and during an insulin infusion at postprandial (PD, 0.15 mU min(-1) 100 ml(-1)) or supraphysiologically high (HD, 0.30 mU min(-1) 100 ml(-1)) doses.Results Leg blood flow, muscle protein synthesis, and Akt/mTOR signalling were not different at baseline. During hyperinsulinaemia, leg blood flow (p < 0.01) and muscle protein synthesis increased in the HD group only (PD [%/h]: from 0.063 +/- 0.006 to 0.060 +/- 0.005; HD [%/h]: from 0.061 +/- 0.007 to 0.098 +/- 0.007; p < 0.01). Muscle Akt phosphorylation increased in both groups, but the increase tended to be greater in the HD group (p = 0.07). The level of p70 ribosomal S6 kinase 1 (S6K1) phosphorylation increased in the HD group only (p < 0.05). Net amino acid balance across the leg improved in both groups, but a net anabolic effect was observed only in the HD group (p < 0.05).Conclusions/interpretation We conclude that supraphysiological hyperinsulinaemia is necessary to stimulate muscle protein synthesis and anabolic signalling in healthy older individuals, suggesting the existence of a true age-related insulin resistance of muscle protein metabolism.

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Insulin substantially stimulates muscle protein synthesis in young people but not in older people.
“Insulin is a powerful anabolic signal and substantially stimulates muscle protein synthesis in young people but not in older people.”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [45]
The age-related insulin resistance of muscle protein synthesis might be overcome by supraphysiological insulin concentrations.
“The age-related insulin resistance of muscle protein synthesis might be overcome by supraphysiological insulin concentrations.45”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [45]

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Authors: Fujita, S., Glynn, E. L., Timmerman, K. L., Rasmussen, B. B., & Volpi, E.
Affiliations: The University of Texas Medical Branch at Galveston (US)
Corresponding author: Volpi, E.
ORCID: Glynn, E. L.
Timmerman, K. L.
Rasmussen, B. B.
Volpi, E.
Venue: Diabetologia
Publisher: Springer Science and Business Media LLC
Published: 2009-07-09
Volume: 52
Issue: 9
Pages: 1889-1898
ISSN: 0012-186X (ISSN-L)
1432-0428
DOI: 10.1007/s00125-009-1430-8
PMC: PMC2843438
OpenAlex: W1972128335
Cited by: 164
References: 47
Citations by year: 2026: 6 · 2025: 6 · 2024: 12 · 2023: 2 · 2022: 10 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 15 · 2015: 10 · 2014: 7 · 2013: 14 · 2012: 8
FWCI: 4.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Diabetologia (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (AG024832)
National Institute on Aging (AG024832, R01AG018311, R01 AG18311, P30AG024832)
National Center for Research Resources (M01 RR-00073, M01 RR-00043, S10RR016650, S10-RR-16650, M01RR000043, M01RR000073)
NIH Clinical Center
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: hyperinsulinemia, insulin resistance, muscle protein synthesis, aging, older adults, Akt/mTOR signaling, leg blood flow, amino acid kinetics, postprandial insulin, glucose tolerance
MeSH terms: Animals, Biopsy, Blood Glucose, Female, Femoral Artery, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Leg, Male, Metabolism, Muscle Proteins, Reference Values, Regional Blood Flow, Body Mass Index, Muscle, Skeletal

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Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: evidence of a true age-related insulin resistance of muscle protein metabolism

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