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Aims <p>Islet transplantation has emerged as a therapeutic option for patients with unstable type 1 diabetes (T1D), but significant islet loss during the peri-transplant period—primarily due to inflammation and substrate deprivation stress—limits its efficacy. Photobiomodulation (PBM), a non-invasive therapy using red or near-infrared light to modulate cellular metabolism, has shown promise in enhancing cell survival under stress. However, its impact on pancreatic beta cells and islets under specific stress conditions remains insufficiently characterized. This study aimed to evaluate the protective and functional effects of PBM (670&#xa0;nm LED light, 2.8 mW/cm²) when applied as a preconditioning or simultaneous treatment on pancreatic beta cells (MIN6) and rat islets exposed to two major types of stress encountered during islet transplantation: substrate deprivation and inflammatory cytokines. The hypothesis tested was that PBM could improve cell viability and insulin secretion under these stress conditions.</p> Methods <p>A series of in vitro experiments were conducted using MIN6 cells and isolated rat islets. PBM was applied either for 24&#xa0;h before or during stress exposure. Substrate deprivation stress (SDS) was induced by glucose and serum-free medium, while cytokine stress involved incubation with IL-1β, TNF-α, and IFN-γ. Outcomes assessed included cell viability (flow cytometry and confocal microscopy), insulin secretion (GSIS assay), mitochondrial function (mitochondrial membrane potential (MMp), superoxide content, oxygen consumption), and cellular energy metabolism (ATP/ADP content via HPLC). Statistical significance was evaluated using ANOVA and post-hoc tests, with <i>p</i> &lt; 0.05 considered significant.</p> Results <p>PBM significantly preserved viability in both MIN6 cells and islets subjected to SDS and cytokine stress. Under SDS, PBM mitigated increases in superoxide production and declines in mitochondrial membrane potential and ATP content in MIN6 cells but did not restore insulin secretion or mitochondrial respiration. In cytokine-stressed cells and islets, PBM restored glucose-stimulated insulin secretion and reduced superoxide content but did not significantly impact MMP or ATP/ADP ratios. Protective effects varied by the timing of PBM application and the type of stress, with some differences observed between cell lines and intact islets.</p> Conclusions <p>PBM exerts beneficial effects on pancreatic beta cell and islet viability and function under stress conditions relevant to islet transplantation, although its mechanisms appear to differ depending on the type of stress. These findings support further investigation into PBM as a preconditioning strategy to enhance islet survival and functionality, potentially improving outcomes in islet transplantation for patients with T1D.</p>

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Impact of photobiomodulation on beta cells and Islets under stress conditions

  • 期刊论文

  • 发表日期：

    2025年11月10日

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  • Quentin Perrier,
  • Cécile Cottet-Rousselle,
  • Frederic Lamarche,
  • Cindy Tellier,
  • Emily Tubbs,
  • Guillaume Vial,
  • Cécile Moro,
  • Sandrine Lablanche

摘要

Aims

Islet transplantation has emerged as a therapeutic option for patients with unstable type 1 diabetes (T1D), but significant islet loss during the peri-transplant period—primarily due to inflammation and substrate deprivation stress—limits its efficacy. Photobiomodulation (PBM), a non-invasive therapy using red or near-infrared light to modulate cellular metabolism, has shown promise in enhancing cell survival under stress. However, its impact on pancreatic beta cells and islets under specific stress conditions remains insufficiently characterized. This study aimed to evaluate the protective and functional effects of PBM (670 nm LED light, 2.8 mW/cm²) when applied as a preconditioning or simultaneous treatment on pancreatic beta cells (MIN6) and rat islets exposed to two major types of stress encountered during islet transplantation: substrate deprivation and inflammatory cytokines. The hypothesis tested was that PBM could improve cell viability and insulin secretion under these stress conditions.

Methods

A series of in vitro experiments were conducted using MIN6 cells and isolated rat islets. PBM was applied either for 24 h before or during stress exposure. Substrate deprivation stress (SDS) was induced by glucose and serum-free medium, while cytokine stress involved incubation with IL-1β, TNF-α, and IFN-γ. Outcomes assessed included cell viability (flow cytometry and confocal microscopy), insulin secretion (GSIS assay), mitochondrial function (mitochondrial membrane potential (MMp), superoxide content, oxygen consumption), and cellular energy metabolism (ATP/ADP content via HPLC). Statistical significance was evaluated using ANOVA and post-hoc tests, with p < 0.05 considered significant.

Results

PBM significantly preserved viability in both MIN6 cells and islets subjected to SDS and cytokine stress. Under SDS, PBM mitigated increases in superoxide production and declines in mitochondrial membrane potential and ATP content in MIN6 cells but did not restore insulin secretion or mitochondrial respiration. In cytokine-stressed cells and islets, PBM restored glucose-stimulated insulin secretion and reduced superoxide content but did not significantly impact MMP or ATP/ADP ratios. Protective effects varied by the timing of PBM application and the type of stress, with some differences observed between cell lines and intact islets.

Conclusions

PBM exerts beneficial effects on pancreatic beta cell and islet viability and function under stress conditions relevant to islet transplantation, although its mechanisms appear to differ depending on the type of stress. These findings support further investigation into PBM as a preconditioning strategy to enhance islet survival and functionality, potentially improving outcomes in islet transplantation for patients with T1D.