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Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.

Rahuljeet S Chadha1, Benjamin Yang1, Dongqiang Yuan2

  • 1Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 26, 2025
PubMed
Summary

Endothelial cells in diabetes store excess glucose as glycogen, which fuels them during starvation. This glycogen metabolism may offer new therapeutic targets for diabetes-induced endothelial dysfunction.

Keywords:
endothelial dysfunctionglutamine and lactate metabolismmetabolic imagingstimulated Raman imagingsubcellular glycogen

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Area of Science:

  • Cellular metabolism
  • Diabetes research
  • Cardiovascular science

Background:

  • Endothelial dysfunction (ED) is central to diabetes mellitus (DM) and metabolic diseases.
  • Endothelial cells (ECs) primarily use glucose, but their glycogen metabolism is poorly understood.
  • Lack of tools hinders investigation into EC glycogen's role.

Purpose of the Study:

  • Investigate glycogen metabolism in live ECs under diabetes-mimicking conditions.
  • Characterize glycogen dynamics and its role as an energy reserve.
  • Explore alternative substrate metabolism in ECs using novel imaging techniques.

Main Methods:

  • Stimulated Raman scattering (SRS) microscopy for live cell imaging.
  • Exposure of ECs to high glucose and TNF-α.
  • Pulse-chase experiments and GSK3 inhibition.

Main Results:

  • ECs store excess glucose as glycogen, enhanced by GSK3 inhibition.
  • Glycogen is rapidly mobilized during glucose starvation, serving as an energy reserve.
  • SRS microscopy visualized glutamine and lactate metabolism in ECs for the first time.
  • Glycogen-rich ECs showed reduced demand for alternative substrates.

Conclusions:

  • Glycogen metabolism in ECs plays a regulatory role in stress adaptation.
  • Targeting EC glycogen may offer therapeutic strategies for diabetes-induced ED.
  • SRS microscopy provides new insights into EC metabolic flexibility.