The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Modulation of insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in liver and muscle of dexamethasone-treated rats.
Open accessAbstract
Insulin rapidly stimulates tyrosine kinase activity of its receptor resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1), which in turn associates with phosphatidylinositol 3-kinase (PI 3-kinase), thus activating the enzyme. Glucocorticoid treatment is known to produce insulin resistance, but the exact molecular mechanism is unknown. In the present study we have examined the levels and phosphorylation state of the insulin receptor and IRS-1, as well as the association/activation between IRS-1 and PI 3-kinase in the liver and muscle of rats treated with dexamethasone. After dexamethasone treatment (1 mg/kg per d for 5 d), there was no change in insulin receptor concentration in liver of rats as determined by immunoblotting with antibody to the COOH-terminus of the receptor. However, insulin stimulation of receptor autophosphorylation determined by immunoblotting with antiphosphotyrosine antibody was reduced by 46.7 +/- 9.1%. IRS-1 and PI 3-kinase protein levels increased in liver of dexamethasone-treated animals by 73 and 25%, respectively (P < 0.05). By contrast, IRS-1 phosphorylation was decreased by 31.3 +/- 10.9% (P < 0.05), and insulin stimulated PI 3-kinase activity in anti-IRS-1 immunoprecipitates was decreased by 79.5 +/- 11.2% (P < 0.02). In muscle, the changes were less dramatic, and often in opposite direction of those observed in liver. Thus, there was no significant change in insulin receptor level or phosphorylation after dexamethasone treatment. IRS-1 and PI 3-kinase levels were decreased to 38.6 and 65.6%, respectively (P < 0.01 and P < 0.05). IRS-1 phosphorylation showed no significant change in muscle, but insulin-stimulated IRS-1 associated PI 3-kinase was decreased by 41%. Thus, dexamethasone has differential effects on the proteins involved in the early steps in insulin action in liver and muscle. In both tissues, dexamethasone treatment results in a reduction in insulin-stimulated IRS-1-associated P I3-kinase, which may play a role in the pathogenesis of insulin resistance at the cellular level in these animals.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“GCs were shown to interfere with insulin signalling in vitro and in vivo in rodents in liver [38], adipose tissue [39] and skeletal muscle [40].”
From Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial (2011) · cites this paper as [40]
Experimental — accuracy not yet measuredIn the citing paper
“Dexamethasone-induced insulin resistance does not alter tyrosine phosphorylation of the insulin receptor [18,26]”
In the citing paper
“but inhibits insulin-stimulated IRS-1 associated PI 3-kinase activity [26].”
In the citing paper
“This concentration has previously been reported to induce a state of insulin resistance [16,26].”
In the citing paper
“whereas dexamethasone treatment reduces IRS-1-associated PI 3-kinase activity [26].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.9.4350 · Cited by 53,218
Raza, H., John, A., & Nemmar, A. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350087 · Cited by 47,311
SH2 and SH3 Domains: Elements that Control Interactions of Cytoplasmic Signaling Proteins
Koch, C. A., Anderson, D. H., Moran, M. F., Ellis, C. A., & Pawson, T. J. (1991) · Science · doi:10.1126/science.1708916 · Cited by 1,868
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., Goldstein, B. J., & White, M. F. (1991) · Nature · doi:10.1038/352073a0 · Cited by 1,574
Self-citationInsulin Stimulates the Phosphorylation of the 95,000-Dalton Subunit of Its Own Receptor
Kasuga, M., Karlsson, F. A., & Kahn, C. R. (1982) · Science · doi:10.1126/science.7031900 · Cited by 1,132
Self-citationPhosphatidylinositol 3′‐kinase is activated by association with IRS‐1 during insulin stimulation.
Backer, J., Myers, M. G., Shoelson, S. E., Chin, D. J., Sun, X., Miralpeix, M., Hu, P. J., Margolis, B. L., Skolnik, E. Y., & Schlessinger, J. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05426.x · Cited by 1,000
Rosen, O. M. (1987) · Science · doi:10.1126/science.2442814 · Cited by 676
Insulin rapidly stimulates tyrosine phosphorylation of a Mr-185,000 protein in intact cells
White, M. F., Maron, R., & Kahn, C. R. (1985) · Nature · doi:10.1038/318183a0 · Cited by 642
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–346 of 346
Leptin and insulin as adiposity signals
Niswender, K. D. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511541643.005
Kinase cascades in the regulation of glucose homeostasis
Steiler, T. L. (2005) · Figshare
Alberto-Silva, C., & Guirro, R. R. D. J. (2000) · Medicina (Ribeirão Preto) · doi:10.11606/issn.2176-7262.v33i4p490-498
Novel pharmaceutical approaches to regulate glucose homeostasis
Sundbom, M. (2010) · Figshare
The role of glucocorticoid receptors and mitogen-regulated protein kinases in the cochlea
Meltser, I. (2009) · Figshare
Einfluss der Histon Deacetylase 6 auf den Glucocorticoid Rezeptor-vermittelten Glucosestoffwechsel
Winkler, R. (2012) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-4337
Han, J. (2008) · VTechWorks (Virginia Tech)
atualização Vias de Sinalização da Insulina
Zecchin, H. G., & Saad, M. J. A. (2002)
Self-citationGedruckt mit Genehmigung des Fachbereichs Veterinärmedizin der Freien Universität Berlin
Brunnberg, L., Staufenbiel, R., Zessin, K.-H., & Fries, R. (2009)
Huang, T., Zheng, J., Mojica, N., & Li, D. (2013) · Current Proteomics · doi:10.2174/15701646112099990004
The impact of glucocorticoids upon the insulin sensitivity of skeletal muscle
Morgan, S. (2010) · University of Birmingham Institutional Research Archive (University of Birmingham)
Insulin Receptor Substrate (IRS-1)
Salajegheh, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-28140-7_28
de Paula, F. J. A., Dick‐de‐Paula, I., Kawai, M., & Rosen, C. J. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415853-5.00040-6
Insulin receptor sensitization improves affective pathology in various mouse models
Nunes, J. P. D. C. A. V. (2015) · doi:10.26481/dis.20151221jc
Clapp, E. L. (2010) · OpenGrey (Institut de l'Information Scientifique et Technique)
Molecular Regulation of Gluconeogenesis by the Nuclear Receptors GR and LXRβ
Patel, R. (2015) · TSpace (University of Toronto)
Some reproductive hormones in relation to ovarian activity in rats
Aboul-Ela, A., El‐Anwar, A. H., Mabrouk, E. A., & Aboul-Khair, A. (2018) · Journal of Veterinary Medical Research · doi:10.21608/jvmr.2017.43323
Investigating the amyloidogenic potential of serum amyloid a in type ii diabetes mellitus
Thomson, G. J. A. (2019) · SUNScholar (Stellenbosch University)
The Expression of the Insulin Receptor Substrate-1 (IRS-1) and Analysis of its Mechanism
Shichiri, M., & Araki, E. (1995) · Folia Endocrinologica Japonica · doi:10.1507/endocrine1927.71.1_21
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2018) · Endocrinology · doi:10.1007/978-3-319-27316-7_19-1
de Paula, F. J. A., Dick‐de‐Paula, I., Kawai, M., & Rosen, C. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-813073-5.00034-4
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2020) · Endocrinology · doi:10.1007/978-3-030-36694-0_19
Ação anti-inflamatória da insulina
Mittestainer, F. C. (2011) · doi:10.47749/t/unicamp.2011.849615
Filho, C. (2005) · doi:10.47749/t/unicamp.2005.380971
Diabètes pharmaco-induits : quatre classes médicamenteuses au cœur de notre pratique clinique
Scheen, A. J., & Fève, B. (2022) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2022.06.004
del Azuay, U., Jerves-Andrade, M., Ruilova-González, L., del Azuay, U., Duque, G., & del Azuay, U. (2022) · doi:10.33324/ceuazuay.227
Steroid hormones and infection and immunity
Kumar, R. A., & McEwan, I. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-91141-2.00008-8
Hyperglycémies iatrogènes en dehors du virus de l’immunodéficience humaine
Treca, P., & Amouyal, C. (2025) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(24)46693-6
Delangre, E. (2021) · theses.fr (ABES) · doi:10.70675/622d48edz59dcz427ez85c9z9da5f8129e84
Glucocorticoid receptor activity in triple negative breast cancer
Noureddine, L. M. (2022) · theses.fr (ABES) · doi:10.70675/13ab50cfz7edbz4a44z918aza657b9614a4d
Peixe, C. D. M. S., Evangelista-Silva, P. H., Giusti‐Paiva, A., Bordin, S. A., & Rafacho, A. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118236
Diabetes Mellitus: Review of the Common, Rare, and Uncommon (Conceptual and Metaphorical) Types
Pliszka, M., & Szablewski, L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27219611
AVALIAÇÃO DO SINAL INSULÍNICO EM RATOS ADULTOS COM LESÃO PERIAPICAL
Astolphi, R. D. (2013) · Americanae (AECID Library)
Metadata
- Authors
- Saad, M. J., Folli, F., Kahn, J. A., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Brigham and Women's Hospital (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1993-10-01
- Volume
- 92
- Issue
- 4
- Pages
- 2065-2072
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288376
- OpenAlex
- W1986519087
- Cited by
- 349
- References
- 42
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 14 · 2019: 2 · 2018: 11 · 2017: 10 · 2016: 14 · 2015: 9 · 2014: 15 · 2013: 12 · 2012: 12
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- Joslin Diabetes Center
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health (DK 36836)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 33201, DK36836, R01DK033201, P30DK036836)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- insulin resistance, glucocorticoids, dexamethasone, insulin receptor, IRS-1, phosphatidylinositol 3-kinase, insulin receptor autophosphorylation, IRS-1 phosphorylation, liver, skeletal muscle, insulin signaling, insulin receptor tyrosine kinase, tissue-specific effects, rats, enzyme activity
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Dexamethasone, Insulin, Kinetics, Liver, Male, Molecular Sequence Data, Muscles, Peptides, Phosphoproteins, Phosphorylation, Receptor, Insulin, Tyrosine, Immunoblotting, Phosphotransferases (Alcohol Group Acceptor), Phosphotyrosine, Phosphatidylinositol 3-Kinases, Rats, Insulin Receptor Substrate Proteins
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
