Related Experiment Video

Updated: Dec 9, 2025

Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
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Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle

Published on: January 19, 2017

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

Thiago M Batista1, Ashok Kumar Jayavelu2, Nicolai J Wewer Albrechtsen3

  • 1Section of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

Cell Metabolism
|September 5, 2020
PubMed

Insights

Skeletal muscle insulin resistance in type 2 diabetes (T2D) may stem from primary cell defects. This study used a disease-in-a-dish model to reveal cell-autonomous signaling flaws in T2D muscle cells.

Area of Science:

  • Cell biology
  • Metabolic diseases
  • Molecular biology

Background:

  • Skeletal muscle insulin resistance is an early indicator of type 2 diabetes (T2D).
  • It is unclear whether this insulin resistance is a primary defect or secondary to systemic factors.
  • Understanding the cellular basis of T2D is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the cell-autonomous defects in skeletal muscle cells from type 2 diabetes patients.
  • To explore the signaling pathways affected in T2D muscle cells using an in vitro model.
  • To identify novel molecular targets for T2D therapy.

Main Methods:

  • Developed an in vitro disease-in-a-dish model using induced pluripotent stem cells (iPSCs) from T2D patients.
  • Differentiated T2D iPSCs into myoblasts (iMyos).
  • Performed global phosphoproteomic analysis to identify signaling pathway alterations.

Main Results:

  • T2D iMyos exhibited impaired insulin signaling and reduced glucose uptake.
  • Mitochondrial oxidation was decreased in T2D iMyos.
  • Phosphoproteomic analysis revealed widespread signaling defects beyond canonical insulin pathways, including Rho GTPase regulation, mRNA processing, and chromatin remodeling.

Conclusions:

  • T2D skeletal muscle cells possess intrinsic, cell-autonomous defects.
  • A complex network of signaling dysregulation contributes to insulin resistance in T2D.
  • These findings offer new insights into the cellular mechanisms underlying type 2 diabetes.
Keywords:
chromatin remodelingglucose transportiPSCinsulin resistancemRNA splicingmitochondrial oxidationphosphoproteomicsskeletal muscletype 2 diabetesvesicle trafficking

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