Abstract 19899: Insulin Treatment Induces Oxidative Stress in the Vascular Wall of Patients With Atherosclerosis Independently of Diabetes or Systemic Insulin Resistance: The Protective Role of DPP-IV Inhibition

Background: Insulin has protective roles in vascular cells, but its vascular effects in patients with atherosclerosis are unknown. We investigate the direct effects of insulin on human vascular redox signaling, and its' interaction with dipeptidyl peptidase IV inhibitors (DPPIV-i). Methods: Saphenous vein (SV) and internal mammary artery (IMA) segements obtained from 72 patients undergoing coronary bypass surgery, were incubated with insulin glargine active metabolite M1 (insulin), insulin degludec (DEG) and human insulin (HI) (1-100nM as stated), +/- pre-incubation with DPPIV-i KR62436 70μM. Vascular superoxide (O2.-) was quantified by lucigenin chemiluminescence, and nitric oxide bioavailability by acetylcholine vasorelaxations ex vivo. Results: Insulin increased NADPH-oxidases-derived O2.- in SV and IMA from diabetics and non-diabetics, effects reversed in vessels from patients treated with oral DPPIV-i (A). Pre-incubation of these vessels with DPPIV-i reversed this effect of insulin (B), improving eNO...