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

S. Fujita, E. L. Glynn, K. L. Timmerman, Blake Rasmussen, Elena Volpi

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1889-1898
Number of pages10
JournalDiabetologia
Volume52
Issue number9
DOIs
StatePublished - Sep 2009

Fingerprint

Muscle Proteins
Hyperinsulinism
Insulin Resistance
Skeletal Muscle
Leg
Phosphorylation
Insulin
70-kDa Ribosomal Protein S6 Kinases
Anabolic Agents
Amino Acids
Glucose
Proto-Oncogene Proteins c-akt
Sirolimus
Immunoblotting
Volunteers
Coloring Agents
Muscles

Keywords

  • Ageing
  • Insulin
  • Insulin resistance
  • Muscle protein synthesis
  • Sarcopenia

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{393c030887514044aef6011c973a9e6f,
title = "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",
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.",
keywords = "Ageing, Insulin, Insulin resistance, Muscle protein synthesis, Sarcopenia",
author = "S. Fujita and Glynn, {E. L.} and Timmerman, {K. L.} and Blake Rasmussen and Elena Volpi",
year = "2009",
month = "9",
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language = "English (US)",
volume = "52",
pages = "1889--1898",
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T1 - Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults

T2 - Evidence of a true age-related insulin resistance of muscle protein metabolism

AU - Fujita, S.

AU - Glynn, E. L.

AU - Timmerman, K. L.

AU - Rasmussen, Blake

AU - Volpi, Elena

PY - 2009/9

Y1 - 2009/9

N2 - 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.

AB - 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.

KW - Ageing

KW - Insulin

KW - Insulin resistance

KW - Muscle protein synthesis

KW - Sarcopenia

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