Circulating extracellular vesicle-carried PTP1B and PP2A phosphatases as regulators of insulin resistance
2025

Role of Extracellular Vesicles in Insulin Resistance

Sample size: 67 publication 10 minutes Evidence: high

Author Information

Author(s): Sakina Ali, Xavier Vidal-Gómez, Megan Piquet, Luisa Vergori, Gilles Simard, Séverine Dubois, Pierre-Henri Ducluzeau, Pascal Pomiès, Sarah Kamli-Salino, Mirela Delibégovic, Samir Henni, Frédéric Gagnadoux, Ramaroson Andriantsitohaina, M. Carmen Martínez

Primary Institution: Université d'Angers

Hypothesis

Extracellular vesicles (EVs) may play an important role in the regulation of metabolic signalling pathways in insulin resistance and associated complications.

Conclusion

Inhibition of phosphatases carried by EVs from insulin-resistant participants rescues insulin signalling in adipocytes and hepatocytes, suggesting these phosphatases as potential therapeutic targets against insulin resistance.

Supporting Evidence

  • Injection of lEVs and sEVs from IR participants impaired insulin signalling in mice.
  • lEVs and sEVs from IR participants increased adipocyte size and adipogenic gene expression.
  • Blockade of PTP1B activity in IR lEVs restored insulin signalling in adipocytes.
  • Blockade of PP2A activity in IR sEVs prevented insulin resistance in adipocytes.
  • IR lEVs were enriched in the active form of PTP1B.
  • IR sEVs were enriched in PP2A.

Takeaway

This study found that tiny bubbles called extracellular vesicles from people with insulin resistance can make it harder for the body to use insulin, which is important for controlling blood sugar.

Methodology

Circulating large and small EVs from individuals with and without insulin resistance were isolated and characterized, then administered to mice to analyze insulin signalling.

Potential Biases

Race and ethnicity data were not available in this study.

Limitations

The study only analyzed the effects of EVs from insulin-resistant individuals on male mice; effects in female mice remain to be determined.

Participant Demographics

67 participants identified as insulin resistant and 38 as non-insulin resistant, with no race or ethnicity data provided.

Statistical Information

P-Value

p=0.8126

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1007/s00125-024-06288-0

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