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A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
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β cell responses to inflammation.

Sahar Usmani-Brown1, Ana Luisa Perdigoto2, Nathalie Lavoie1

  • 1Department of L2 Diagnostics, New Haven, CT, USA.

Molecular Metabolism
|September 11, 2019
PubMed
Summary

Detecting beta cell death in vivo is crucial for understanding Type 1 diabetes (T1D) pathogenesis. New assays show promise but require further development for early detection in at-risk individuals.

Keywords:
ApoptosisBeta cellsDeathInflammationMethylationType 1 diabetes

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Area of Science:

  • Immunology
  • Endocrinology
  • Molecular Biology

Background:

  • Type 1 diabetes (T1D) progression is often silent, complicating early intervention.
  • Beta cell adaptive changes influence immunogenicity and susceptibility to autoimmune destruction.
  • Traditional methods for detecting beta cell loss rely on functional impairment, which can be affected by environmental factors.

Purpose of the Study:

  • To review methods for detecting beta cell death in vivo, particularly in inflammatory conditions.
  • To highlight beta cell responses to cell death during T1D development.

Main Methods:

  • Development of a novel assay to measure beta cell death in vivo.
  • Detection of cell-free DNA with INS gene epigenetic modifications specific to beta cells.
  • Analysis of data from the Diabetes Prevention Trial-1.

Main Results:

  • The developed assay demonstrates robust technical performance in identifying beta cell killing in high-risk individuals.
  • Assay sensitivity is limited in at-risk relatives due to short cell-free DNA half-life and need for repeated sampling.
  • Identified adaptive beta cell changes that may avoid immune destruction but impair function, potentially representing a recoverable cell source.

Conclusions:

  • The novel assay is a valuable tool for detecting beta cell death in vivo, especially in high-risk populations.
  • Further refinement is needed to improve detection in early-stage or at-risk individuals.
  • Understanding adaptive beta cell responses is key to developing new therapeutic strategies for T1D.