Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle

Zhengping Yi, Paul R Langlais, Elena Anna De Filippis, Moulun Luo, Charles R. Flynn, Stefanie Schroeder, Susan T. Weintraub, Rebekka Mapes, Lawrence J. Mandarino

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

OBJECTIVE - Research has focused on insulin receptor substrate (IRS)-1 as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Of 1,242 amino acids in IRS-1, 242 are serine/threonine. Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans. RESEARCH DESIGN AND METHODS - In this study, we describe our use of capillary high-performance liquid chromotography electrospray tandem mass spectrometry to identify/quantify site-specific phosphorylation of IRS-1 in human vastus lateralis muscle obtained by needle biopsy basally and after insulin infusion in four healthy volunteers. RESULTS - Twenty-two serine/threonine phosphorylation sites were identified; 15 were quantified. Three sites had not been previously identified (Thr495, Ser 527, and S1005). Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 (2.6 ± 0.4, 2.9 ± 0.8, 2.1 ± 0.3, 1.6 ± 0.1, 1.3 ± 0.1, and 1.3 ± 0.1-fold, respectively, compared with basal; P < 0.05); phosphorylation of Ser 348, Thr446, Thr495, and Ser1005 decreased (0.4 ± 0.1, 0.2 ± 0.1, 0.1 ± 0.1, and 0.3 ± 0.2-fold, respectively; P < 0.05). CONCLUSIONS - These results provide an assessment of IRS-1 phosphorylation in vivo and show that insulin has profound effects on IRS-1 serine/threonine phosphorylation in healthy humans.

Original languageEnglish (US)
Pages (from-to)1508-1516
Number of pages9
JournalDiabetes
Volume56
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

Fingerprint

Insulin Receptor Substrate Proteins
Phosphorylation
Insulin
Threonine
Muscles
Serine
Quadriceps Muscle
Needle Biopsy
Tandem Mass Spectrometry
Tyrosine
Insulin Resistance
Healthy Volunteers
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. / Yi, Zhengping; Langlais, Paul R; De Filippis, Elena Anna; Luo, Moulun; Flynn, Charles R.; Schroeder, Stefanie; Weintraub, Susan T.; Mapes, Rebekka; Mandarino, Lawrence J.

In: Diabetes, Vol. 56, No. 6, 06.2007, p. 1508-1516.

Research output: Contribution to journalArticle

Yi, Z, Langlais, PR, De Filippis, EA, Luo, M, Flynn, CR, Schroeder, S, Weintraub, ST, Mapes, R & Mandarino, LJ 2007, 'Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle', Diabetes, vol. 56, no. 6, pp. 1508-1516. https://doi.org/10.2337/db06-1355
Yi, Zhengping ; Langlais, Paul R ; De Filippis, Elena Anna ; Luo, Moulun ; Flynn, Charles R. ; Schroeder, Stefanie ; Weintraub, Susan T. ; Mapes, Rebekka ; Mandarino, Lawrence J. / Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle. In: Diabetes. 2007 ; Vol. 56, No. 6. pp. 1508-1516.
@article{99fac5e4e20f4b8e863903cf9992a0bd,
title = "Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle",
abstract = "OBJECTIVE - Research has focused on insulin receptor substrate (IRS)-1 as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Of 1,242 amino acids in IRS-1, 242 are serine/threonine. Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans. RESEARCH DESIGN AND METHODS - In this study, we describe our use of capillary high-performance liquid chromotography electrospray tandem mass spectrometry to identify/quantify site-specific phosphorylation of IRS-1 in human vastus lateralis muscle obtained by needle biopsy basally and after insulin infusion in four healthy volunteers. RESULTS - Twenty-two serine/threonine phosphorylation sites were identified; 15 were quantified. Three sites had not been previously identified (Thr495, Ser 527, and S1005). Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 (2.6 ± 0.4, 2.9 ± 0.8, 2.1 ± 0.3, 1.6 ± 0.1, 1.3 ± 0.1, and 1.3 ± 0.1-fold, respectively, compared with basal; P < 0.05); phosphorylation of Ser 348, Thr446, Thr495, and Ser1005 decreased (0.4 ± 0.1, 0.2 ± 0.1, 0.1 ± 0.1, and 0.3 ± 0.2-fold, respectively; P < 0.05). CONCLUSIONS - These results provide an assessment of IRS-1 phosphorylation in vivo and show that insulin has profound effects on IRS-1 serine/threonine phosphorylation in healthy humans.",
author = "Zhengping Yi and Langlais, {Paul R} and {De Filippis}, {Elena Anna} and Moulun Luo and Flynn, {Charles R.} and Stefanie Schroeder and Weintraub, {Susan T.} and Rebekka Mapes and Mandarino, {Lawrence J.}",
year = "2007",
month = "6",
doi = "10.2337/db06-1355",
language = "English (US)",
volume = "56",
pages = "1508--1516",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "6",

}

TY - JOUR

T1 - Global assessment of regulation of phosphorylation of insulin receptor substrate-1 by insulin in vivo in human muscle

AU - Yi, Zhengping

AU - Langlais, Paul R

AU - De Filippis, Elena Anna

AU - Luo, Moulun

AU - Flynn, Charles R.

AU - Schroeder, Stefanie

AU - Weintraub, Susan T.

AU - Mapes, Rebekka

AU - Mandarino, Lawrence J.

PY - 2007/6

Y1 - 2007/6

N2 - OBJECTIVE - Research has focused on insulin receptor substrate (IRS)-1 as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Of 1,242 amino acids in IRS-1, 242 are serine/threonine. Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans. RESEARCH DESIGN AND METHODS - In this study, we describe our use of capillary high-performance liquid chromotography electrospray tandem mass spectrometry to identify/quantify site-specific phosphorylation of IRS-1 in human vastus lateralis muscle obtained by needle biopsy basally and after insulin infusion in four healthy volunteers. RESULTS - Twenty-two serine/threonine phosphorylation sites were identified; 15 were quantified. Three sites had not been previously identified (Thr495, Ser 527, and S1005). Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 (2.6 ± 0.4, 2.9 ± 0.8, 2.1 ± 0.3, 1.6 ± 0.1, 1.3 ± 0.1, and 1.3 ± 0.1-fold, respectively, compared with basal; P < 0.05); phosphorylation of Ser 348, Thr446, Thr495, and Ser1005 decreased (0.4 ± 0.1, 0.2 ± 0.1, 0.1 ± 0.1, and 0.3 ± 0.2-fold, respectively; P < 0.05). CONCLUSIONS - These results provide an assessment of IRS-1 phosphorylation in vivo and show that insulin has profound effects on IRS-1 serine/threonine phosphorylation in healthy humans.

AB - OBJECTIVE - Research has focused on insulin receptor substrate (IRS)-1 as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Of 1,242 amino acids in IRS-1, 242 are serine/threonine. Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans. RESEARCH DESIGN AND METHODS - In this study, we describe our use of capillary high-performance liquid chromotography electrospray tandem mass spectrometry to identify/quantify site-specific phosphorylation of IRS-1 in human vastus lateralis muscle obtained by needle biopsy basally and after insulin infusion in four healthy volunteers. RESULTS - Twenty-two serine/threonine phosphorylation sites were identified; 15 were quantified. Three sites had not been previously identified (Thr495, Ser 527, and S1005). Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 (2.6 ± 0.4, 2.9 ± 0.8, 2.1 ± 0.3, 1.6 ± 0.1, 1.3 ± 0.1, and 1.3 ± 0.1-fold, respectively, compared with basal; P < 0.05); phosphorylation of Ser 348, Thr446, Thr495, and Ser1005 decreased (0.4 ± 0.1, 0.2 ± 0.1, 0.1 ± 0.1, and 0.3 ± 0.2-fold, respectively; P < 0.05). CONCLUSIONS - These results provide an assessment of IRS-1 phosphorylation in vivo and show that insulin has profound effects on IRS-1 serine/threonine phosphorylation in healthy humans.

UR - http://www.scopus.com/inward/record.url?scp=34249661732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249661732&partnerID=8YFLogxK

U2 - 10.2337/db06-1355

DO - 10.2337/db06-1355

M3 - Article

C2 - 17360977

AN - SCOPUS:34249661732

VL - 56

SP - 1508

EP - 1516

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -