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Amelioration of Diabetes by Protein S

Taro Yasuma1, Yutaka Yano1, Corina N D'Alessandro-Gabazza2

  • 1Department of Diabetes, Metabolism and Endocrinology, Mie University Graduate School of Medicine, Edobashi, Japan.

Diabetes
|May 22, 2016
PubMed

Insights

Protein S, an anticoagulant factor, improves blood glucose control and insulin sensitivity in diabetes. It also protects against diabetic nephropathy by reducing beta-cell apoptosis.

Area of Science:

  • Endocrinology
  • Nephrology
  • Molecular Biology

Background:

  • Protein S is known for its anticoagulant properties and roles in inflammation and apoptosis.
  • The impact of Protein S on diabetes and its complications remained largely unexplored.

Purpose of the Study:

  • To investigate the effects of Protein S on diabetes development and diabetic glomerulosclerosis.
  • To explore the therapeutic potential of Protein S in managing diabetes and its renal complications.

Main Methods:

  • Comparison of diabetes development in wild-type and Protein S-overexpressing transgenic mice.
  • Assessment of exogenous Protein S administration on insulin sensitivity in cell lines and diabetic mice.
  • Evaluation of Protein S's impact on islet beta-cell apoptosis and glomerulosclerosis severity.

Main Results:

  • Protein S overexpression significantly improved glucose levels, glucose tolerance, insulin sensitivity, and insulin secretion in mice.
  • Exogenous Protein S enhanced insulin sensitivity in adipocytes, skeletal muscle, and liver cells.
  • Protein S inhibited apoptosis in islet beta-cells, increasing BIRC3 and Bcl-2 expression and Akt/PKB activation.
  • Protein S treatment and overexpression reduced the severity of diabetic glomerulosclerosis.
  • Lower circulating free Protein S levels were observed in patients with type 2 diabetes.

Conclusions:

  • Protein S plays a protective role in attenuating diabetes and its complications.
  • Protein S demonstrates therapeutic potential by inhibiting beta-cell apoptosis and preventing diabetic nephropathy.

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