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10.3390/cells10092237
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Article

Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus

by
Yuko Okano
1,2,†,
Atsuro Takeshita
1,2,†,
Taro Yasuma
1,2,†,
Masaaki Toda
1,
Kota Nishihama
2,
Valeria Fridman D’Alessandro
1,
Chisa Inoue
2,
Corina N. D’Alessandro-Gabazza
1,
Tetsu Kobayashi
3,
Yutaka Yano
2 and
Esteban C. Gabazza
1,*
1
Department of Immunology, Faculty and Graduate School of Medicine, Mie University, Tsu 514-8507, Mie, Japan
2
Department of Diabetes and Endocrinology, Faculty and Graduate School of Medicine, Mie University, Tsu 514-8507, Mie, Japan
3
Department of Pulmonary and Critical Care Medicine, Faculty and Graduate School of Medicine, Mie University, Tsu 514-8507, Mie, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2021, 10(9), 2237; https://doi.org/10.3390/cells10092237
Submission received: 17 July 2021 / Revised: 23 August 2021 / Accepted: 25 August 2021 / Published: 29 August 2021
(This article belongs to the Special Issue Cellular and Molecular Biology of the Beta Cell)
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Abstract

Diabetes mellitus is a global threat to human health. The ultimate cause of diabetes mellitus is insufficient insulin production and secretion associated with reduced pancreatic β-cell mass. Apoptosis is an important and well-recognized mechanism of the progressive loss of functional β-cells. However, there are currently no available antiapoptotic drugs for diabetes mellitus. This study evaluated whether recombinant human thrombomodulin can inhibit β-cell apoptosis and improve glucose intolerance in a diabetes mouse model. A streptozotocin-induced diabetes mouse model was prepared and treated with thrombomodulin or saline three times per week for eight weeks. The glucose tolerance and apoptosis of β-cells were evaluated. Diabetic mice treated with recombinant human thrombomodulin showed significantly improved glucose tolerance, increased insulin secretion, decreased pancreatic islet areas of apoptotic β-cells, and enhanced proportion of regulatory T cells and tolerogenic dendritic cells in the spleen compared to counterpart diseased mice treated with saline. Non-diabetic mice showed no changes. This study shows that recombinant human thrombomodulin, a drug currently used to treat patients with coagulopathy in Japan, ameliorates glucose intolerance by protecting pancreatic islet β-cells from apoptosis and modulating the immune response in diabetic mice. This observation points to recombinant human thrombomodulin as a promising antiapoptotic drug for diabetes mellitus.
Keywords: insulin resistance; diabetes mellitus; apoptosis; thrombomodulin; glucose intolerance; immune cells insulin resistance; diabetes mellitus; apoptosis; thrombomodulin; glucose intolerance; immune cells

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MDPI and ACS Style

Okano, Y.; Takeshita, A.; Yasuma, T.; Toda, M.; Nishihama, K.; Fridman D’Alessandro, V.; Inoue, C.; D’Alessandro-Gabazza, C.N.; Kobayashi, T.; Yano, Y.; et al. Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus. Cells 2021, 10, 2237. https://doi.org/10.3390/cells10092237

AMA Style

Okano Y, Takeshita A, Yasuma T, Toda M, Nishihama K, Fridman D’Alessandro V, Inoue C, D’Alessandro-Gabazza CN, Kobayashi T, Yano Y, et al. Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus. Cells. 2021; 10(9):2237. https://doi.org/10.3390/cells10092237

Chicago/Turabian Style

Okano, Yuko, Atsuro Takeshita, Taro Yasuma, Masaaki Toda, Kota Nishihama, Valeria Fridman D’Alessandro, Chisa Inoue, Corina N. D’Alessandro-Gabazza, Tetsu Kobayashi, Yutaka Yano, and et al. 2021. "Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus" Cells 10, no. 9: 2237. https://doi.org/10.3390/cells10092237

APA Style

Okano, Y., Takeshita, A., Yasuma, T., Toda, M., Nishihama, K., Fridman D’Alessandro, V., Inoue, C., D’Alessandro-Gabazza, C. N., Kobayashi, T., Yano, Y., & Gabazza, E. C. (2021). Protective Role of Recombinant Human Thrombomodulin in Diabetes Mellitus. Cells, 10(9), 2237. https://doi.org/10.3390/cells10092237

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