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Morpho-Functional Responsiveness of Caco-2 Enterocyte-like Monolayers to Insulin in a Pro-Inflammatory Environment

Aurora Mazzei1, Marina Damato2, Ilenia Iaia3

  • 1Laboratory of Applied Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

Cells
|September 13, 2025
PubMed

Insights

Insulin (INS) influences intestinal epithelial cell structure and function. Its effects vary depending on inflammatory signals like interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ), impacting cytoskeletal organization and cell responses.

Area of Science:

  • Cell Biology
  • Gastroenterology
  • Endocrinology

Background:

  • Insulin (INS) regulates nutrient metabolism and affects target cell morphology, including cytoskeletal actin.
  • Insulin sensitivity impacts intestinal epithelial cells, influencing tight junctions and barrier permeability.
  • The physiological role of insulin in gastrointestinal epithelia requires further elucidation.

Purpose of the Study:

  • To investigate insulin's effects on differentiated Caco-2 intestinal cell monolayers under inflammatory conditions (IL-1β and IFN-γ).
  • To identify morpho-functional changes in intestinal epithelia in response to insulin and specific inflammatory mediators.
  • To understand how insulin signaling interacts with inflammatory pathways to modulate intestinal cell structure and function.

Main Methods:

  • Cultured differentiated Caco-2 cell monolayers.
  • Challenged monolayers with pro-inflammatory cytokines: interleukin 1 beta (IL-1β) and interferon gamma (IFN-γ).
  • Assessed insulin's impact on actin cytoskeleton organization and expression of related proteins (FAK, ITGB1) and the MAPK signaling pathway.

Main Results:

  • Insulin significantly altered actin cytoskeleton organization in Caco-2 cells.
  • Pro-inflammatory stimuli (IL-1β, IFN-γ) modulated insulin's effects on cell morphology.
  • Synergistic action of IFN-γ and insulin altered expression of cytoskeletal proteins (FAK, ITGB1) and impacted MAPK signaling.

Conclusions:

  • Intestinal epithelial cells exhibit a modular response to insulin, influenced by different inflammatory mediators.
  • Insulin signaling plays a role in the morpho-functional remodeling of intestinal epithelial cells.
  • There is a significant interplay between insulin signaling and inflammatory responses in regulating intestinal epithelial cell behavior.

Keywords:
Caco-2 monolayersinflammationinsulin signaling pathwaysintestinal epithelium

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