| First Author | Yasuma T | Year | 2016 |
| Journal | Diabetes | Volume | 65 |
| Issue | 7 | Pages | 1940-51 |
| PubMed ID | 27207541 | Mgi Jnum | J:246871 |
| Mgi Id | MGI:5923039 | Doi | 10.2337/db15-1404 |
| Citation | Yasuma T, et al. (2016) Amelioration of Diabetes by Protein S. Diabetes 65(7):1940-51 |
| abstractText | 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 beta-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 beta-cells and the development of diabetic nephropathy. |
