Endothelial peNOS signaling and ET‐1 mRNA expression during acute hyperinsulinemia in type 2 diabetes (1072.5)

Increased endothelin‐1 (ET‐1) and reduced endothelial nitric oxide production are thought to play a role in vascular dysfunction in type 2 diabetes (T2D). However, little is known in humans about changes in endothelial signaling in response to insulin stimulation. Therefore, endothelial nitric oxide synthase (eNOS) signaling and ET‐1 expression were measured from vastus lateralis skeletal muscle biopsies taken before and 60 min into a hyperinsulinemic euglycemic clamp in 6 healthy controls (body fat: 22.8±3.6 %, glucose disposal rate (GDR): 12.6±2.4 mg/kg lean body mass (LBM)/min) and 5 T2D (body fat: 43.4±4.6%, GDR: 6.7±2.5mg/kg LBM/min). Muscle samples were analyzed for pAKT (ser473), AKT, peNOS (ser1177) and eNOS protein and ET‐1 mRNA expression. In response to insulin, peNOS/eNOS was not significantly different between groups (controls: 1.13±0.22, T2D: 0.69±0.31 fold change from baseline; p>0.05). The increase in ET‐1 mRNA from baseline (controls: 1.0±0.4, T2D: 3.4±1.4, p>0.05) was also not different during insulin stimulation (controls: 1.3±0.7, T2D: 2.1±0.9, p>0.05). However, the fold increase of pAKT/AKT to hyperinsulinemia was significantly different between groups (controls: 3.1±0.4, T2D: 1.8±0.4, p=0.002). These initial findings suggest that insulin‐mediated phosphorylation of eNOS protein and induction of ET‐1 mRNA are not significantly different between healthy and T2D individuals. Grant Funding Source : Supported by AHA 12PRE12080242(LJB)