Global IRS-1 phosphorylation analysis in insulin resistance

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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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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. R., Yi, Z., Finlayson, J., Luo, M., Mapes, R., De Filippis, E. A., ... 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, Paul R; Yi, Z.; Finlayson, J.; Luo, M.; Mapes, R.; De Filippis, Elena Anna; 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, PR, Yi, Z, Finlayson, J, Luo, M, Mapes, R, De Filippis, EA, 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, Paul R ; Yi, Z. ; Finlayson, J. ; Luo, M. ; Mapes, R. ; De Filippis, Elena Anna ; 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.
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AU - Luo, M.

AU - Mapes, R.

AU - De Filippis, Elena Anna

AU - Meyer, C.

AU - Plummer, E.

AU - Tongchinsub, P.

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KW - Threonine

KW - Type 2 diabetes

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