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Cited by 169Muscle metabolism and nutritionMetabolism, Diabetes, and CancerMuscle Physiology and Disorders

Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle

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Louard, R J, Fryburg, D A, Gelfand, R A, Barrett, E J·1992·Journal of Clinical Investigation
DOI 10.1172/jci116124PMC PMC443389
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Abstract

Physiologic increases of insulin promote net amino acid uptake and protein anabolism in forearm skeletal muscle by restraining protein degradation. The sensitivity of this process to insulin is not known. Using the forearm perfusion method, we infused insulin locally in the brachial artery at rates of 0.00 (saline control), 0.01, 0.02, 0.035, or 0.05 mU/min per kg for 150 min to increase local forearm plasma insulin concentration by 0, approximately 20, approximately 35, approximately 60, and approximately 120 microU/ml (n = 35). L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine were infused systemically, and the net forearm balance, rate of appearance (Ra) and rate of disposal (R(d)) of phenylalanine and leucine, and forearm glucose balance were measured basally and in response to insulin infusion. Compared to saline, increasing rates of insulin infusion progressively increased net forearm glucose uptake from 0.9 mumol/min per 100 ml (saline) to 1.0, 1.8, 2.4, and 4.7 mumol/min per 100 ml forearm, respectively. Net forearm balance for phenylalanine and leucine was significantly less negative than basal (P < 0.01 for each) in response to the lowest dose insulin infusion, 0.01 mU/min per kg, and all higher rates of insulin infusion. Phenylalanine and leucine R(a) declined by approximately 38 and 40% with the lowest dose insulin infusion. Higher doses of insulin produced no greater effect (decline in R(a) varied between 26 and 42% for phenylalanine and 30-50% for leucine). In contrast, R(d) for phenylalanine and leucine did not change with insulin. We conclude that even modest increases of plasma insulin can markedly suppress proteolysis, measured by phenylalanine R(a), in human forearm skeletal muscle. Further increments of insulin within the physiologic range augment glucose uptake but have little additional effect on phenylalanine R(a) or balance. These results suggest that proteolysis in human skeletal muscle is more sensitive than glucose uptake to physiologic increments in insulin.

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Authors
Louard, R. J., Fryburg, D. A., Gelfand, R. A., & Barrett, E. J.
Affiliations
  • Yale University (US)
  • University of Virginia Health System (US)
  • Pfizer (United States) (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1992-12-01
Volume
90
Issue
6
Pages
2348-2354
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci116124
PMC
PMC443389
OpenAlex
W1968028970
Semantic Scholar
8e9d3212afeaaf85a46eb3ffed9a8ddc23da6c4c
Cited by
169
References
36
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 5 · 2013: 2 · 2012: 5
FWCI
2.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
insulin sensitivity, skeletal muscle, protein metabolism, glucose uptake, amino acid metabolism, phenylalanine, leucine, proteolysis, insulin infusion, muscle protein anabolism
MeSH terms
Adult, Amino Acids, Arm, Female, Glucose, Humans, Insulin, Leucine, Male, Muscle Proteins, Muscles, Phenylalanine, Regional Blood Flow

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