Role of insulin receptor phosphorylation in the insulinomimetic effects of hydrogen peroxide.

Hayes, G R; Lockwood, D H

doi:10.1073/pnas.84.22.8115

Cited by 155Metabolism, Diabetes, and CancerRedox biology and oxidative stressAdipokines, Inflammation, and Metabolic Diseases

Role of insulin receptor phosphorylation in the insulinomimetic effects of hydrogen peroxide.

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Hayes, G R, Lockwood, D H·1987·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.84.22.8115PMC PMC299489

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Abstract

The oxidant H2O2 has many insulin-like effects in rat adipocytes. To determine whether these effects could be mediated by the tyrosine kinase activity of the insulin receptor, the ability of H2O2 to stimulate receptor phosphorylation in intact adipocytes and partially purified insulin receptors has been examined. Phosphorylation of the beta subunit of the insulin receptor was increased approximately 2-fold by treatment of intact cells with 3 mM H2O2, a concentration that maximally stimulates 2-deoxyglucose uptake. Stimulation of receptor phosphorylation was rapid, reaching maximal levels within 5 min, and preceded activation of glucose transport. Phosphoamino acid analysis of insulin receptors from H2O2-treated adipocytes showed that 32P incorporation into phosphotyrosine and phosphoserine residues of the beta subunit was enhanced. Furthermore, partially purified receptors from H2O2-treated cells exhibit increased tyrosine kinase activity, as measured by phosphorylation of the peptide Glu80Tyr20. In contrast, the direct addition of H2O2 to partially purified insulin receptors did not stimulate tyrosine kinase activity or insulin receptor autophosphorylation. This was not due to breakdown of H2O2 or oxidation of ATP or the required divalent cations. To define the factors involved in H2O2's effect, we have examined receptor phosphorylation in fat cell homogenates and purified plasma membranes. Although insulin stimulated receptor phosphorylation in both of these systems, H2O2 was only effective in the cell homogenates. These data demonstrate that, under certain conditions, H2O2 stimulates insulin receptor phosphorylation and tyrosine kinase activity, suggesting that the insulin-like effects of H2O2 may be mediated by stimulation of insulin receptor phosphorylation. This does not appear to be a direct effect of H2O2 on the insulin receptor and requires nonplasma membrane cellular constituents.

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Authors: Hayes, G. R., & Lockwood, D. H.
Affiliations: University of Rochester Medicine (US)
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1987-11
Volume: 84
Issue: 22
Pages: 8115-8119
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.84.22.8115
PMC: PMC299489
OpenAlex: W2028078288
Cited by: 155
References: 36
Citations by year: 2025: 1 · 2024: 1 · 2021: 1 · 2020: 4 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 8 · 2012: 5
FWCI: 2.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01am020129-10)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: insulin receptor, receptor phosphorylation, hydrogen peroxide, adipocytes, tyrosine kinase activity, insulin receptor beta-subunit, glucose transport, 2-deoxyglucose uptake, phosphotyrosine, phosphoserine, insulin receptor autophosphorylation, oxidative stress, insulin signaling
MeSH terms: Adipose Tissue, Animals, Deoxyglucose, Epididymis, Hydrogen Peroxide, Insulin, Male, Oxidation-Reduction, Phosphorylation, Protein-Tyrosine Kinases, Rats, Inbred Strains, Receptor, Insulin, Rats

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Role of insulin receptor phosphorylation in the insulinomimetic effects of hydrogen peroxide.

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