The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Inhibition of Protein Kinase Cβ Prevents Impaired Endothelium-Dependent Vasodilation Caused by Hyperglycemia in Humans
Abstract
The bioavailability of nitric oxide is decreased in animal models and humans with diabetes mellitus. Hyperglycemia, in particular, attenuates endothelium-dependent vasodilation in healthy subjects. In vitro and in vivo animal studies implicate activation of protein kinase Cβ as an important mechanism whereby hyperglycemia decreases endothelium-derived nitric oxide. Accordingly, this study tested the hypothesis that inhibition of protein kinase Cβ would prevent impairment of endothelium-dependent vasodilation in healthy humans exposed to hyperglycemia. This study was a randomized, double-blind, placebo-controlled, crossover trial. Healthy subjects were treated with an orally active, selective, protein kinase Cβ inhibitor, LY333531, or matching placebo once a day for 7 days before vascular function testing. Forearm blood flow was measured using venous-occlusion, strain-gauge plethysmography. Endothelium-dependent vasodilation was measured via incremental brachial artery administration of methacholine chloride (0.3 to 10 μg/min) during euglycemia and after 6 hours of hyperglycemic clamp. The forearm blood flow dose-response curve to methacholine was significantly attenuated by hyperglycemia after placebo treatment ( P =0.009 by ANOVA, euglycemia versus hyperglycemia) but not after treatment with LY333531. Inhibition of protein kinase Cβ prevents the reduction in endothelium-dependent vasodilation induced by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia impairs endothelial function, in part, via protein kinase Cβ activation.
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1 retracted
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RetractedNormalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
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The extended protein kinase C superfamily
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Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus
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Self-citation
Cited by
The clinical implications of endothelial dysfunction
Widlansky, M. E., Gokce, N., Keaney, J. F., & Vita, J. A. (2003) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(03)00994-x · Cited by 1,749
Diabetes and Vascular Disease: Pathophysiology, Clinical Consequences, and Medical Therapy: Part I
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Self-citationActivation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications
Geraldes, P., & King, G. L. (2010) · Circulation Research · doi:10.1161/circresaha.110.217117 · Cited by 985
Cardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 872
Du, X., Matsumura, T., Edelstein, D., Rossetti, L., Zsengellér, Z., Szabó, C., & Brownlee, M. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18127 · Cited by 832
Metadata
- Authors
- Beckman, J. A., Goldfine, A. B., Gordon, M. B., Garrett, L. A., & Creager, M. A.
- Venue
- Circulation Research
- Published
- 2002-01-11
- Volume
- 90
- Issue
- 1
- Pages
- 107-111
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2000625731
- Cited by
- 277
- References
- 48
- FWCI
- 13.23
- Type
- journal article
- Language
- en
- Open access
- closed
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