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Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions

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Abstract

The objective of the present study was to determine the effects of glucagon-like peptide-1 (GLP-1) on barrier functions and to assess the underlying mechanism using an in vitro blood-brain barrier (BBB) model comprised of a primary culture of rat brain capillary endothelial cells (RBECs). GLP-1 increased transendothelial electrical resistance and decreased the permeability of sodium fluorescein in RBECs in a dose- and time-dependent manner. The effects on these barrier functions were significantly reduced in the presence of the GLP-1 receptor antagonist exendin-3 (9–39) and the protein kinase A (PKA) inhibitor H-89. Western blot analysis showed that GLP-1 increased the amount of occludin and claudin-5. GLP-1 analogs are approved for treatment of type 2 diabetes mellitus, and thus, we examined the effects of GLP-1 on hyperglycemia-induced BBB damage. GLP-1 inhibited the increase in production of reactive oxygen species under hyperglycemia conditions and improved the BBB integrity induced by hyperglycemia. As GLP-1 stabilized the integrity of the BBB, probably via cAMP/PKA signaling, the possibility that GLP-1 acts as a BBB-protective drug should be considered.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Young Scientists (B) (24790258) from the Japan Society for the Promotion of Science (JSPS). We would like to thank Keisuke Toyoda, Gohei So for their critical reviews of the manuscript and helpful professional guidance.

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Authors and Affiliations

  1. Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Shuji Fukuda, Yoichi Morofuji, Tomonori Takeshita, Kentaro Hayashi & Takayuki Matsuo

  2. Department of Medical Pharmacology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Shinsuke Nakagawa & Rie Tatsumi

  3. Advanced Medical Education Support Center, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

    Kunihiko Tanaka

  4. BBB Laboratory, PharmaCo-Cell Company, Ltd., Nagasaki, 1-43 Dejima, Nagasaki, 850-0862, Japan

    Masami Niwa

Authors
  1. Shuji Fukuda
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  2. Shinsuke Nakagawa
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  3. Rie Tatsumi
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  4. Yoichi Morofuji
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  8. Takayuki Matsuo
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  9. Masami Niwa
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Correspondence to Shinsuke Nakagawa.

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Fukuda, S., Nakagawa, S., Tatsumi, R. et al. Glucagon-Like Peptide-1 Strengthens the Barrier Integrity in Primary Cultures of Rat Brain Endothelial Cells Under Basal and Hyperglycemia Conditions. J Mol Neurosci 59, 211–219 (2016). https://doi.org/10.1007/s12031-015-0696-1

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  • DOI: https://doi.org/10.1007/s12031-015-0696-1

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