Role of adropin in reducing arterial stiffness in type 2 diabetes

Abstract

Adropin is a peptide primarily expressed and secreted by the liver and is known to regulate energy homeostasis. Increasing evidence also indicates that adropin can exert vascular effects and its low circulating levels are associated with increased arterial stiffness, obesity, and type 2 diabetes. However, whether reduced adropin contributes to arterial stiffening in type 2 diabetes remains unknown. Herein, we tested the hypothesis that loss of adropin in non‐diabetic mice causes arterial stiffening and that the converse is also true. That is, adropin exposure reduces arterial stiffness in diabetic mice. In alignment with this hypothesis, we found that 1) mesenteric arteries from adropin knockout male mice are stiffer than those from wild‐type littermates; 2) exposure of human endothelial cells and mesenteric arteries from diabetic (i.e., db/db) male mice to adropin reduces actin polymerization and stiffness; 3) adropin‐induced reduction of actin polymerization and softening of endothelial cells and diabetic arteries is abrogated by inhibition of nitric oxide synthase; and 4) treatment of diabetic male mice with adropin for four weeks reduces arterial stiffness in mesenteric arteries. Collectively, these findings support the notion that reduced adropin may be implicated in arterial stiffening and thus represent a novel therapeutic target to lessen arterial stiffness in type 2 diabetes.