Exposure to adropin improves insulin‐induced dilation in arteries from type 2 diabetic mice

Abstract

Vascular insulin resistance is a hallmark of type 2 diabetes (T2D) and blunting of insulin‐induced dilation is its primary manifestation. Importantly, in T2D, reduced insulin‐induced dilation and blood flow to skeletal muscle significantly limits glucose uptake and contributes to impaired glucose control. However, the mechanisms underlying vascular insulin resistance in T2D remain largely unknown. Adropin is a peptide primarily secreted by the liver and brain, recently shown to regulate energy homeostasis as well as to promote systemic insulin sensitivity. Notably, circulating levels of adropin are decreased in T2D, which may contribute to impairments in vascular insulin signaling. Herein we tested the hypothesis that arterial exposure to adropin improves vascular insulin sensitivity, particularly in T2D. To test this hypothesis, femoral arteries from ~12‐week old db/db (n=5) and genetic control (db+/−, n=5) male mice were incubated with adropin (50 ng/mL) or vehicle for 24 hours and vasomotor responses to acetylcholine, insulin, and sodium nitroprusside (SNP) assessed thereafter via pressure myography. Consistent with our hypothesis, we show that treatment of femoral arteries from db/db mice with adropin improves insulin‐induced dilation (P<0.05), an effect that is not observed in db+/− control mice (P>0.05). Adropin exposure did not alter acetylcholine and SNP‐induced dilation of femoral arteries in either db/db or db+/− mice (P>0.05). These findings support the notion that adropin deficiency may contribute to vascular insulin resistance in T2D.