Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study

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Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes : A case-control study. / Karlsson, Håkan K.R.; Kasahara, Akiko; Ikeda, Mika; Chibalin, Alexander V.; Harada, Jun; Rydén, Mikael; Krook, Anna; Kato, Mitsunori; Kubota, Kazuishi; Zierath, Juleen R.

In: Metabolism, Vol. 118, 154726, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Karlsson, HKR, Kasahara, A, Ikeda, M, Chibalin, AV, Harada, J, Rydén, M, Krook, A, Kato, M, Kubota, K & Zierath, JR 2021, 'Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study', Metabolism, vol. 118, 154726. https://doi.org/10.1016/j.metabol.2021.154726

APA

Karlsson, H. K. R., Kasahara, A., Ikeda, M., Chibalin, A. V., Harada, J., Rydén, M., Krook, A., Kato, M., Kubota, K., & Zierath, J. R. (2021). Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study. Metabolism, 118, [154726]. https://doi.org/10.1016/j.metabol.2021.154726

Vancouver

Karlsson HKR, Kasahara A, Ikeda M, Chibalin AV, Harada J, Rydén M et al. Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study. Metabolism. 2021;118. 154726. https://doi.org/10.1016/j.metabol.2021.154726

Author

Karlsson, Håkan K.R. ; Kasahara, Akiko ; Ikeda, Mika ; Chibalin, Alexander V. ; Harada, Jun ; Rydén, Mikael ; Krook, Anna ; Kato, Mitsunori ; Kubota, Kazuishi ; Zierath, Juleen R. / Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes : A case-control study. In: Metabolism. 2021 ; Vol. 118.

Bibtex

@article{ce6a3bd677b84c32ae6b621776e37a4e,
title = "Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes: A case-control study",
abstract = "Background & aims: The physiological regulation and contribution of the multiple phosphorylation sites of insulin receptor substrate 1 (IRS1) to the pathogenesis of insulin resistance is unknown. Our aims were to map the phosphorylated motifs of IRS1 in skeletal muscle from people with normal glucose tolerance (NGT; n = 11) or type 2 diabetes mellitus (T2DM; n = 11). Methods: Skeletal muscle biopsies were obtained under fasted conditions or during a euglycemic clamp and IRS1 phosphorylation sites were identified by mass spectrometry. Results: We identified 33 phosphorylation sites in biopsies from fasted individuals, including 2 previously unreported sites ([Ser393] and [Thr1017]). In men with NGT and T2DM, insulin increased phosphorylation of 5 peptides covering 10 serine or threonine sites and decreased phosphorylation of 6 peptides covering 9 serine, threonine or tyrosine sites. Insulin-stimulation increased phosphorylation of 2 peptides, and decreased phosphorylation of 2 peptides only in men with NGT. Insulin increased phosphorylation of 2 peptides only in men with T2DM. Conclusions: Despite severe skeletal muscle insulin resistance, the pattern of IRS1 phosphorylation was not uniformly altered in T2DM. Our results contribute to the evolving understanding of the physiological regulation of insulin signaling and complement the comprehensive map of IRS1 phosphorylation in T2DM.",
keywords = "Insulin resistance, Insulin signaling, IRS1, Phosphoproteomics, Skeletal muscle, Type 2 diabetes",
author = "Karlsson, {H{\aa}kan K.R.} and Akiko Kasahara and Mika Ikeda and Chibalin, {Alexander V.} and Jun Harada and Mikael Ryd{\'e}n and Anna Krook and Mitsunori Kato and Kazuishi Kubota and Zierath, {Juleen R.}",
note = "Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
doi = "10.1016/j.metabol.2021.154726",
language = "English",
volume = "118",
journal = "Metabolism",
issn = "0026-0495",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Quantitative phosphoproteomic analysis of IRS1 in skeletal muscle from men with normal glucose tolerance or type 2 diabetes

T2 - A case-control study

AU - Karlsson, Håkan K.R.

AU - Kasahara, Akiko

AU - Ikeda, Mika

AU - Chibalin, Alexander V.

AU - Harada, Jun

AU - Rydén, Mikael

AU - Krook, Anna

AU - Kato, Mitsunori

AU - Kubota, Kazuishi

AU - Zierath, Juleen R.

N1 - Publisher Copyright: © 2021 The Authors

PY - 2021

Y1 - 2021

N2 - Background & aims: The physiological regulation and contribution of the multiple phosphorylation sites of insulin receptor substrate 1 (IRS1) to the pathogenesis of insulin resistance is unknown. Our aims were to map the phosphorylated motifs of IRS1 in skeletal muscle from people with normal glucose tolerance (NGT; n = 11) or type 2 diabetes mellitus (T2DM; n = 11). Methods: Skeletal muscle biopsies were obtained under fasted conditions or during a euglycemic clamp and IRS1 phosphorylation sites were identified by mass spectrometry. Results: We identified 33 phosphorylation sites in biopsies from fasted individuals, including 2 previously unreported sites ([Ser393] and [Thr1017]). In men with NGT and T2DM, insulin increased phosphorylation of 5 peptides covering 10 serine or threonine sites and decreased phosphorylation of 6 peptides covering 9 serine, threonine or tyrosine sites. Insulin-stimulation increased phosphorylation of 2 peptides, and decreased phosphorylation of 2 peptides only in men with NGT. Insulin increased phosphorylation of 2 peptides only in men with T2DM. Conclusions: Despite severe skeletal muscle insulin resistance, the pattern of IRS1 phosphorylation was not uniformly altered in T2DM. Our results contribute to the evolving understanding of the physiological regulation of insulin signaling and complement the comprehensive map of IRS1 phosphorylation in T2DM.

AB - Background & aims: The physiological regulation and contribution of the multiple phosphorylation sites of insulin receptor substrate 1 (IRS1) to the pathogenesis of insulin resistance is unknown. Our aims were to map the phosphorylated motifs of IRS1 in skeletal muscle from people with normal glucose tolerance (NGT; n = 11) or type 2 diabetes mellitus (T2DM; n = 11). Methods: Skeletal muscle biopsies were obtained under fasted conditions or during a euglycemic clamp and IRS1 phosphorylation sites were identified by mass spectrometry. Results: We identified 33 phosphorylation sites in biopsies from fasted individuals, including 2 previously unreported sites ([Ser393] and [Thr1017]). In men with NGT and T2DM, insulin increased phosphorylation of 5 peptides covering 10 serine or threonine sites and decreased phosphorylation of 6 peptides covering 9 serine, threonine or tyrosine sites. Insulin-stimulation increased phosphorylation of 2 peptides, and decreased phosphorylation of 2 peptides only in men with NGT. Insulin increased phosphorylation of 2 peptides only in men with T2DM. Conclusions: Despite severe skeletal muscle insulin resistance, the pattern of IRS1 phosphorylation was not uniformly altered in T2DM. Our results contribute to the evolving understanding of the physiological regulation of insulin signaling and complement the comprehensive map of IRS1 phosphorylation in T2DM.

KW - Insulin resistance

KW - Insulin signaling

KW - IRS1

KW - Phosphoproteomics

KW - Skeletal muscle

KW - Type 2 diabetes

U2 - 10.1016/j.metabol.2021.154726

DO - 10.1016/j.metabol.2021.154726

M3 - Journal article

C2 - 33581131

AN - SCOPUS:85101581407

VL - 118

JO - Metabolism

JF - Metabolism

SN - 0026-0495

M1 - 154726

ER -

ID: 272643004