Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Batista, TM, Jayavelu, AK, Wewer Albrechtsen, NJ, Iovino, S, Lebastchi, J, Pan, H, Dreyfuss, JM, Krook, A, Zierath, JR, Mann, M & Kahn, CR 2020, 'A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes', Cell Metabolism, vol. 32, no. 5, pp. 844-859.e5. https://doi.org/10.1016/j.cmet.2020.08.007

APA

Batista, T. M., Jayavelu, A. K., Wewer Albrechtsen, N. J., Iovino, S., Lebastchi, J., Pan, H., Dreyfuss, J. M., Krook, A., Zierath, J. R., Mann, M., & Kahn, C. R. (2020). A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes. Cell Metabolism, 32(5), 844-859.e5. https://doi.org/10.1016/j.cmet.2020.08.007

CBE

Batista TM, Jayavelu AK, Wewer Albrechtsen NJ, Iovino S, Lebastchi J, Pan H, Dreyfuss JM, Krook A, Zierath JR, Mann M, Kahn CR. 2020. A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes. Cell Metabolism. 32(5):844-859.e5. https://doi.org/10.1016/j.cmet.2020.08.007

MLA

Vancouver

Author

Batista, Thiago M ; Jayavelu, Ashok Kumar ; Wewer Albrechtsen, Nicolai J ; Iovino, Salvatore ; Lebastchi, Jasmin ; Pan, Hui ; Dreyfuss, Jonathan M ; Krook, Anna ; Zierath, Juleen R ; Mann, Matthias ; Kahn, C Ronald. / A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes. In: Cell Metabolism. 2020 ; Vol. 32, No. 5. pp. 844-859.e5.

Bibtex

@article{e3d17be99a44446d859f577c8aae3155,
title = "A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes",
abstract = "Skeletal muscle insulin resistance is the earliest defect in type 2 diabetes (T2D), preceding and predicting disease development. To what extent this reflects a primary defect or is secondary to tissue cross talk due to changes in hormones or circulating metabolites is unknown. To address this question, we have developed an in vitro disease-in-a-dish model using iPS cells from T2D patients differentiated into myoblasts (iMyos). We find that T2D iMyos in culture exhibit multiple defects mirroring human disease, including an altered insulin signaling, decreased insulin-stimulated glucose uptake, and reduced mitochondrial oxidation. More strikingly, global phosphoproteomic analysis reveals a multidimensional network of signaling defects in T2D iMyos going beyond the canonical insulin-signaling cascade, including proteins involved in regulation of Rho GTPases, mRNA splicing and/or processing, vesicular trafficking, gene transcription, and chromatin remodeling. These cell-autonomous defects and the dysregulated network of protein phosphorylation reveal a new dimension in the cellular mechanisms underlying the fundamental defects in T2D.",
keywords = "chromatin remodeling, glucose transport, insulin resistance, iPSC, mitochondrial oxidation, mRNA splicing, phosphoproteomics, skeletal muscle, type 2 diabetes, vesicle trafficking",
author = "Batista, {Thiago M} and Jayavelu, {Ashok Kumar} and {Wewer Albrechtsen}, {Nicolai J} and Salvatore Iovino and Jasmin Lebastchi and Hui Pan and Dreyfuss, {Jonathan M} and Anna Krook and Zierath, {Juleen R} and Matthias Mann and Kahn, {C Ronald}",
note = "Copyright {\textcopyright} 2020. Published by Elsevier Inc.",
year = "2020",
month = nov,
day = "3",
doi = "10.1016/j.cmet.2020.08.007",
language = "English",
volume = "32",
pages = "844--859.e5",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes

AU - Batista, Thiago M

AU - Jayavelu, Ashok Kumar

AU - Wewer Albrechtsen, Nicolai J

AU - Iovino, Salvatore

AU - Lebastchi, Jasmin

AU - Pan, Hui

AU - Dreyfuss, Jonathan M

AU - Krook, Anna

AU - Zierath, Juleen R

AU - Mann, Matthias

AU - Kahn, C Ronald

N1 - Copyright © 2020. Published by Elsevier Inc.

PY - 2020/11/3

Y1 - 2020/11/3

N2 - Skeletal muscle insulin resistance is the earliest defect in type 2 diabetes (T2D), preceding and predicting disease development. To what extent this reflects a primary defect or is secondary to tissue cross talk due to changes in hormones or circulating metabolites is unknown. To address this question, we have developed an in vitro disease-in-a-dish model using iPS cells from T2D patients differentiated into myoblasts (iMyos). We find that T2D iMyos in culture exhibit multiple defects mirroring human disease, including an altered insulin signaling, decreased insulin-stimulated glucose uptake, and reduced mitochondrial oxidation. More strikingly, global phosphoproteomic analysis reveals a multidimensional network of signaling defects in T2D iMyos going beyond the canonical insulin-signaling cascade, including proteins involved in regulation of Rho GTPases, mRNA splicing and/or processing, vesicular trafficking, gene transcription, and chromatin remodeling. These cell-autonomous defects and the dysregulated network of protein phosphorylation reveal a new dimension in the cellular mechanisms underlying the fundamental defects in T2D.

AB - Skeletal muscle insulin resistance is the earliest defect in type 2 diabetes (T2D), preceding and predicting disease development. To what extent this reflects a primary defect or is secondary to tissue cross talk due to changes in hormones or circulating metabolites is unknown. To address this question, we have developed an in vitro disease-in-a-dish model using iPS cells from T2D patients differentiated into myoblasts (iMyos). We find that T2D iMyos in culture exhibit multiple defects mirroring human disease, including an altered insulin signaling, decreased insulin-stimulated glucose uptake, and reduced mitochondrial oxidation. More strikingly, global phosphoproteomic analysis reveals a multidimensional network of signaling defects in T2D iMyos going beyond the canonical insulin-signaling cascade, including proteins involved in regulation of Rho GTPases, mRNA splicing and/or processing, vesicular trafficking, gene transcription, and chromatin remodeling. These cell-autonomous defects and the dysregulated network of protein phosphorylation reveal a new dimension in the cellular mechanisms underlying the fundamental defects in T2D.

KW - chromatin remodeling

KW - glucose transport

KW - insulin resistance

KW - iPSC

KW - mitochondrial oxidation

KW - mRNA splicing

KW - phosphoproteomics

KW - skeletal muscle

KW - type 2 diabetes

KW - vesicle trafficking

UR - http://www.scopus.com/inward/record.url?scp=85091077521&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2020.08.007

DO - 10.1016/j.cmet.2020.08.007

M3 - Journal article

C2 - 32888406

VL - 32

SP - 844-859.e5

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 5

ER -

ID: 61271559