Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex

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Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. / Haider, Nida; Lebastchi, Jasmin; Jayavelu, Ashok Kumar; Batista, Thiago M; Pan, Hui; Dreyfuss, Jonathan M; Carcamo-Orive, Ivan; Knowles, Joshua W; Mann, Matthias; Kahn, C Ronald.

In: The Journal of Clinical Investigation, Vol. 131, No. 21, 01.11.2021.

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

Harvard

Haider, N, Lebastchi, J, Jayavelu, AK, Batista, TM, Pan, H, Dreyfuss, JM, Carcamo-Orive, I, Knowles, JW, Mann, M & Kahn, CR 2021, 'Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex', The Journal of Clinical Investigation, vol. 131, no. 21. https://doi.org/10.1172/JCI151818

APA

Haider, N., Lebastchi, J., Jayavelu, A. K., Batista, T. M., Pan, H., Dreyfuss, J. M., Carcamo-Orive, I., Knowles, J. W., Mann, M., & Kahn, C. R. (2021). Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. The Journal of Clinical Investigation, 131(21). https://doi.org/10.1172/JCI151818

Vancouver

Haider N, Lebastchi J, Jayavelu AK, Batista TM, Pan H, Dreyfuss JM et al. Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. The Journal of Clinical Investigation. 2021 Nov 1;131(21). https://doi.org/10.1172/JCI151818

Author

Haider, Nida ; Lebastchi, Jasmin ; Jayavelu, Ashok Kumar ; Batista, Thiago M ; Pan, Hui ; Dreyfuss, Jonathan M ; Carcamo-Orive, Ivan ; Knowles, Joshua W ; Mann, Matthias ; Kahn, C Ronald. / Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex. In: The Journal of Clinical Investigation. 2021 ; Vol. 131, No. 21.

Bibtex

@article{61c4d3c74cac4d66912e877660f208ad,
title = "Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex",
abstract = "Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.",
keywords = "Diabetes Mellitus, Type 2/metabolism, Female, GTPase-Activating Proteins/metabolism, Humans, Insulin Receptor Substrate Proteins/metabolism, Insulin Resistance, Male, Proto-Oncogene Proteins c-akt/metabolism, Sex Characteristics, Signal Transduction, TOR Serine-Threonine Kinases/metabolism",
author = "Nida Haider and Jasmin Lebastchi and Jayavelu, {Ashok Kumar} and Batista, {Thiago M} and Hui Pan and Dreyfuss, {Jonathan M} and Ivan Carcamo-Orive and Knowles, {Joshua W} and Matthias Mann and Kahn, {C Ronald}",
year = "2021",
month = nov,
day = "1",
doi = "10.1172/JCI151818",
language = "English",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "21",

}

RIS

TY - JOUR

T1 - Signaling defects associated with insulin resistance in nondiabetic and diabetic individuals and modification by sex

AU - Haider, Nida

AU - Lebastchi, Jasmin

AU - Jayavelu, Ashok Kumar

AU - Batista, Thiago M

AU - Pan, Hui

AU - Dreyfuss, Jonathan M

AU - Carcamo-Orive, Ivan

AU - Knowles, Joshua W

AU - Mann, Matthias

AU - Kahn, C Ronald

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.

AB - Insulin resistance is present in one-quarter of the general population, predisposing these people to a wide range of diseases. Our aim was to identify cell-intrinsic determinants of insulin resistance in this population using induced pluripotent stem cell-derived (iPSC-derived) myoblasts (iMyos). We found that these cells exhibited a large network of altered protein phosphorylation in vitro. Integrating these data with data from type 2 diabetic iMyos revealed critical sites of conserved altered phosphorylation in IRS-1, AKT, mTOR, and TBC1D1 in addition to changes in protein phosphorylation involved in Rho/Rac signaling, chromatin organization, and RNA processing. There were also striking differences in the phosphoproteome in cells from men versus women. These sex-specific and insulin-resistance defects were linked to functional differences in downstream actions. Thus, there are cell-autonomous signaling alterations associated with insulin resistance within the general population and important differences between men and women, many of which also occur in diabetes, that contribute to differences in physiology and disease.

KW - Diabetes Mellitus, Type 2/metabolism

KW - Female

KW - GTPase-Activating Proteins/metabolism

KW - Humans

KW - Insulin Receptor Substrate Proteins/metabolism

KW - Insulin Resistance

KW - Male

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Sex Characteristics

KW - Signal Transduction

KW - TOR Serine-Threonine Kinases/metabolism

U2 - 10.1172/JCI151818

DO - 10.1172/JCI151818

M3 - Journal article

C2 - 34506305

VL - 131

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 21

ER -

ID: 303115782