Amelioration of Diabetes by Protein S.

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 wild-type 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.

• Authors: 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
• Journal: Diabetes (Diabetes) Vol. 65 Issue 7 Pg. 1940-51 (07 2016) ISSN: 1939-327X [Electronic] United States
• PMID: 27207541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Blood Glucose
• Protein S

Topics

• Adipocytes (drug effects, metabolism)
• Animals
• Apoptosis (drug effects)
• Blood Glucose (metabolism)
• Cell Line
• Diabetes Mellitus, Experimental (genetics, metabolism)
• Diabetes Mellitus, Type 1 (genetics, metabolism)
• Diabetes Mellitus, Type 2 (genetics, metabolism)
• Diabetic Nephropathies (genetics, metabolism)
• Female
• Glucose Tolerance Test
• Humans
• Insulin Resistance (physiology)
• Insulin-Secreting Cells (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Male
• Mice
• Mice, Transgenic
• Middle Aged
• Muscle, Skeletal (drug effects, metabolism)
• Protein S (genetics, metabolism, pharmacology)