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Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway

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Abstract

Purpose

Human islet amyloid polypeptide (hIAPP) aggregation is linked to loss of pancreatic beta cells in type 2 diabetes, in part due to oxidative stress. Currently, little is known about the effects of selenium-enriched Spirulina on beta cells with the presence of hIAPP. In this study, INS-1E rat insulinoma cells were used as a model to evaluate in vitro protective effects of Se-enriched Spirulina extract (Se-SE) against hIAPP-induced cell death, as well as the underlying mechanisms.

Methods

Flow cytometric analysis was used to evaluate cell apoptosis, mitochondrial membrane potential (ΔΨm) and ROS generation. Caspase activity was measured using a fluorometric method. Western blotting was applied to detect protein expression.

Results

Our results showed that exposure of INS-1E cells to hIAPP resulted in cell viability loss, LDH release and appearance of sub-G peak. However, cytotoxicity of hIAPP was significantly attenuated by co-treatment with Se-SE. Se-SE also inhibited hIAPP-induced activation of caspase-3, -8 and -9. Additionally, hIAPP-induced accumulation of ROS and superoxide was suppressed by co-treatment with Se-SE. Moreover, Se-SE was able to prevent hIAPP-induced depletion of ΔΨm and intracellular ATP, reduction in mitochondrial mass, changes in the expression of Bcl-2 family members, release of mitochondrial apoptogenic factors. Furthermore, hIAPP-mediated AKT inhibition was restored by co-treatment with Se-SE.

Conclusion

Our results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death through preventing ROS overproduction, mitochondrial dysfunction and modulating PI3K/AKT pathway.

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Acknowledgments

The work was supported by the Hong Kong Government Research Grant Committee, Hong Kong Foundation for Research and Development in Diabetes, the Natural Science Foundation of China and Guangdong Province, Program for New Century Excellent Talents in University and China Postdoctoral Science Foundation.

Conflict of interest

The authors have declared no conflict of interest.

Author information

Authors and Affiliations

  1. College of Life Sciences and Technology, Jinan University, Guangzhou, China

    Xiao-Ling Li

  2. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China

    Xiao-Ling Li, Gang Xu & Juliana C. N. Chan

  3. School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

    Yum-Shing Wong

  4. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China

    Juliana C. N. Chan

  5. Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, China

    Juliana C. N. Chan

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  1. Xiao-Ling Li
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  2. Yum-Shing Wong
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  4. Juliana C. N. Chan
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Correspondence to Juliana C. N. Chan.

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Li, XL., Wong, YS., Xu, G. et al. Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway. Eur J Nutr 54, 509–522 (2015). https://doi.org/10.1007/s00394-014-0732-x

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  • DOI: https://doi.org/10.1007/s00394-014-0732-x

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