Global IRS-1 phosphorylation analysis in insulin resistance

P. Langlais, Z. Yi, J. Finlayson, M. Luo, R. Mapes, E. De Filippis, C. Meyer, E. Plummer, P. Tongchinsub, M. Mattern, L. J. Mandarino

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Aims/hypothesis: IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo. Methods: We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers. Results: Basal Ser323 phosphorylation was increased in type 2 diabetic patients (2.1 ± 0.43, p ≤ 0.05, fold change vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic patients (p ≤ 0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4 ± 0.17, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3 ± 0.16, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56 ± 0.11, p ≤ 0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64 ± 0.16, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77 ± 0.22, p ≤ 0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3 ± 0.2, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal). Conclusions/interpretation: We conclude that, unlike some aspects of insulin signalling, the ability of insulin to increase or suppress certain IRS-1 phosphorylation sites is intact in insulin resistance. However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.

    Original languageEnglish (US)
    Pages (from-to)2878-2889
    Number of pages12
    JournalDiabetologia
    Volume54
    Issue number11
    DOIs
    StatePublished - Nov 2011

    Fingerprint

    Insulin Resistance
    Phosphorylation
    Insulin
    Muscles
    Quadriceps Muscle
    Serine
    Volunteers
    High Pressure Liquid Chromatography

    Keywords

    • Insulin resistance
    • IRS-1
    • Mass spectrometry
    • Phosphorylation
    • Serine
    • Threonine
    • Type 2 diabetes

    ASJC Scopus subject areas

    • Internal Medicine
    • Endocrinology, Diabetes and Metabolism

    Cite this

    Langlais, P., Yi, Z., Finlayson, J., Luo, M., Mapes, R., De Filippis, E., ... Mandarino, L. J. (2011). Global IRS-1 phosphorylation analysis in insulin resistance. Diabetologia, 54(11), 2878-2889. https://doi.org/10.1007/s00125-011-2271-9

    Global IRS-1 phosphorylation analysis in insulin resistance. / Langlais, P.; Yi, Z.; Finlayson, J.; Luo, M.; Mapes, R.; De Filippis, E.; Meyer, C.; Plummer, E.; Tongchinsub, P.; Mattern, M.; Mandarino, L. J.

    In: Diabetologia, Vol. 54, No. 11, 11.2011, p. 2878-2889.

    Research output: Contribution to journalArticle

    Langlais, P, Yi, Z, Finlayson, J, Luo, M, Mapes, R, De Filippis, E, Meyer, C, Plummer, E, Tongchinsub, P, Mattern, M & Mandarino, LJ 2011, 'Global IRS-1 phosphorylation analysis in insulin resistance', Diabetologia, vol. 54, no. 11, pp. 2878-2889. https://doi.org/10.1007/s00125-011-2271-9
    Langlais P, Yi Z, Finlayson J, Luo M, Mapes R, De Filippis E et al. Global IRS-1 phosphorylation analysis in insulin resistance. Diabetologia. 2011 Nov;54(11):2878-2889. https://doi.org/10.1007/s00125-011-2271-9
    Langlais, P. ; Yi, Z. ; Finlayson, J. ; Luo, M. ; Mapes, R. ; De Filippis, E. ; Meyer, C. ; Plummer, E. ; Tongchinsub, P. ; Mattern, M. ; Mandarino, L. J. / Global IRS-1 phosphorylation analysis in insulin resistance. In: Diabetologia. 2011 ; Vol. 54, No. 11. pp. 2878-2889.
    @article{3325ed404b354bbb8eb663310ecca841,
    title = "Global IRS-1 phosphorylation analysis in insulin resistance",
    abstract = "Aims/hypothesis: IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo. Methods: We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers. Results: Basal Ser323 phosphorylation was increased in type 2 diabetic patients (2.1 ± 0.43, p ≤ 0.05, fold change vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic patients (p ≤ 0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4 ± 0.17, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3 ± 0.16, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56 ± 0.11, p ≤ 0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64 ± 0.16, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77 ± 0.22, p ≤ 0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3 ± 0.2, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal). Conclusions/interpretation: We conclude that, unlike some aspects of insulin signalling, the ability of insulin to increase or suppress certain IRS-1 phosphorylation sites is intact in insulin resistance. However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.",
    keywords = "Insulin resistance, IRS-1, Mass spectrometry, Phosphorylation, Serine, Threonine, Type 2 diabetes",
    author = "P. Langlais and Z. Yi and J. Finlayson and M. Luo and R. Mapes and {De Filippis}, E. and C. Meyer and E. Plummer and P. Tongchinsub and M. Mattern and Mandarino, {L. J.}",
    year = "2011",
    month = "11",
    doi = "10.1007/s00125-011-2271-9",
    language = "English (US)",
    volume = "54",
    pages = "2878--2889",
    journal = "Diabetologia",
    issn = "0012-186X",
    publisher = "Springer Verlag",
    number = "11",

    }

    TY - JOUR

    T1 - Global IRS-1 phosphorylation analysis in insulin resistance

    AU - Langlais, P.

    AU - Yi, Z.

    AU - Finlayson, J.

    AU - Luo, M.

    AU - Mapes, R.

    AU - De Filippis, E.

    AU - Meyer, C.

    AU - Plummer, E.

    AU - Tongchinsub, P.

    AU - Mattern, M.

    AU - Mandarino, L. J.

    PY - 2011/11

    Y1 - 2011/11

    N2 - Aims/hypothesis: IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo. Methods: We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers. Results: Basal Ser323 phosphorylation was increased in type 2 diabetic patients (2.1 ± 0.43, p ≤ 0.05, fold change vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic patients (p ≤ 0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4 ± 0.17, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3 ± 0.16, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56 ± 0.11, p ≤ 0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64 ± 0.16, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77 ± 0.22, p ≤ 0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3 ± 0.2, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal). Conclusions/interpretation: We conclude that, unlike some aspects of insulin signalling, the ability of insulin to increase or suppress certain IRS-1 phosphorylation sites is intact in insulin resistance. However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.

    AB - Aims/hypothesis: IRS-1 serine phosphorylation is often elevated in insulin resistance models, but confirmation in vivo in humans is lacking. We therefore analysed IRS-1 phosphorylation in human muscle in vivo. Methods: We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers. Results: Basal Ser323 phosphorylation was increased in type 2 diabetic patients (2.1 ± 0.43, p ≤ 0.05, fold change vs lean controls). Thr495 phosphorylation was decreased in type 2 diabetic patients (p ≤ 0.05). Insulin increased IRS-1 phosphorylation at Ser527 (1.4 ± 0.17, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3 ± 0.16, p ≤ 0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56 ± 0.11, p ≤ 0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64 ± 0.16, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77 ± 0.22, p ≤ 0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3 ± 0.2, p ≤ 0.05, fold change, 60 min after insulin infusion vs basal). Conclusions/interpretation: We conclude that, unlike some aspects of insulin signalling, the ability of insulin to increase or suppress certain IRS-1 phosphorylation sites is intact in insulin resistance. However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.

    KW - Insulin resistance

    KW - IRS-1

    KW - Mass spectrometry

    KW - Phosphorylation

    KW - Serine

    KW - Threonine

    KW - Type 2 diabetes

    UR - http://www.scopus.com/inward/record.url?scp=80054707320&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=80054707320&partnerID=8YFLogxK

    U2 - 10.1007/s00125-011-2271-9

    DO - 10.1007/s00125-011-2271-9

    M3 - Article

    VL - 54

    SP - 2878

    EP - 2889

    JO - Diabetologia

    JF - Diabetologia

    SN - 0012-186X

    IS - 11

    ER -