1. Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress J Am Coll Cardiol. 2001;38(7):1821-1828. doi:10.1016/S0735-1097(01)01659-X Figure Legend: Percent changes in left anterior descending artery (LAD) diameters from baseline values in response to intracoronary infusion of graded dose (50 μg, 100 μg) of acetylcholine (ACh) and to 0.3 mg of nitroglycerin (NTG) categorized by tertiles of insulin sensitivity in patients with normal coronary angiogram (n = 36). IS = insulin sensitive (open bars); BL = borderline (solid bars); IR = insulin resistant (hatched bars). *p < 0.05 vs. IS. †p < 0.05 vs. BL.

2. Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress J Am Coll Cardiol. 2001;38(7):1821-1828. doi:10.1016/S0735-1097(01)01659-X Figure Legend: Correlation between percent changes in left anterior descending artery (LAD) diameters from baseline values in response to intracoronary infusion of 100 μg acetylcholine (ACh) and 2-h insulin area, plasma lipid hydroperoxide (TBARS) level of coronary sinus-arterial (CS-Ao) difference, BH 4 /7,8-BH 2 + biopterin, and dihydropteridine reductase (DHPR) activity in study subjects (n = 36). BH 4 = tetrahydrobiopterin; BH 2 = dihydrobiopterin.

3. Date of download: 9/19/2016 Copyright © The American College of Cardiology. All rights reserved. From: Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress J Am Coll Cardiol. 2001;38(7):1821-1828. doi:10.1016/S0735-1097(01)01659-X Figure Legend: Hypothetical scheme illustrating the possible mechanism of impaired endothelial function in the insulin-resistant state. Increased quinonoid dihydrobiopterin (qBH 2 ) synthesis in the insulin-resistant state is closely associated with a decrement in the activity of dihydropteridine reductase (DHPR), the recycling enzyme that converts BH 2 to tetrahydrobiopterin (BH 4 ). As a result, both BH 4 /BH 2 ratio and BH 4 to total biopterin (BH 2 + BH 4 ) were significantly decreased in the insulin-resistant subjects. These results indicate that decreased nitric oxide (NO)- dependent vasodilation in the insulin-resistant state may be related to abnormal pteridine metabolism and vascular oxidative stress. GTP = guanosine triphosphate; eNOS = endothelial nitric oxide synthase; O 2 − = superoxide anion; PTPS = 6-pyruvoyltetrahydropterine synthase; SR = sepiapterin reductase.