Amelioration of diabetes by protein S

Taro Yasuma, Yutaka Yano, Corina N. D'Alessandro-Gabazza, Masaaki Toda, Paloma Gil-Bernabe, Tetsu Kobayashi, Kota Nishihama, Josephine A. Hinneh, Rumi Mifuji-Moroka, Ziaurahman Roeen, John Morser, Isaac Cann, Iwasa Motoh, Yoshiyuki Takei, Esteban C. Gabazza

Research output: Contribution to journalArticle

Abstract

Protein S is an anticoagulant factor that also regulates inflammation and cell apoptosis. The effect of protein S on diabetes and its complications is unknown. This study compared the development of diabetes between wildtype and transgenic mice overexpressing human protein S and the development of diabetic glomerulosclerosis between mice treated with and without human protein S and between wild-type and protein S transgenic mice. Mice overexpressing protein S showed significant improvements in blood glucose level, glucose tolerance, insulin sensitivity, and insulin secretion compared with wild-type counterparts. Exogenous protein S improved insulin sensitivity in adipocytes, skeletal muscle, and liver cell lines in db/db mice compared with controls. Significant inhibition of apoptosis with increased expression of BIRC3 and Bcl-2 and enhanced activation of Akt/PKB was induced by protein S in islet β-cells compared with controls. Diabetic wild-type mice treated with protein S and diabetic protein S transgenic mice developed significantly less severe diabetic glomerulosclerosis than controls. Patients with type 2 diabetes had significantly lower circulating free protein S than healthy control subjects. This study shows that protein S attenuates diabetes by inhibiting apoptosis of β-cells and the development of diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)1940-1951
Number of pages12
JournalDiabetes
Volume65
Issue number7
DOIs
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Yasuma, T., Yano, Y., D'Alessandro-Gabazza, C. N., Toda, M., Gil-Bernabe, P., Kobayashi, T., Nishihama, K., Hinneh, J. A., Mifuji-Moroka, R., Roeen, Z., Morser, J., Cann, I., Motoh, I., Takei, Y., & Gabazza, E. C. (2016). Amelioration of diabetes by protein S. Diabetes, 65(7), 1940-1951. https://doi.org/10.2337/db15-1404