A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes

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

Standard

A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes. / 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.

In: Cell Metabolism, Vol. 32, No. 5, 2020, p. 844-859.e5.

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

Vancouver

Batista TM, Jayavelu AK, Wewer Albrechtsen NJ, Iovino S, Lebastchi J, Pan H et al. A Cell-Autonomous Signature of Dysregulated Protein Phosphorylation Underlies Muscle Insulin Resistance in Type 2 Diabetes. Cell Metabolism. 2020;32(5):844-859.e5. https://doi.org/10.1016/j.cmet.2020.08.007

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{1abe84326493464d9577a3b94361b898,

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.",

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",

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

PY - 2020

Y1 - 2020

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.

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: 248762180