Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress
- 1 March 2012
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 32 (3), 712-720
- https://doi.org/10.1161/atvbaha.111.227389
Abstract
Objective—: Hypoglycemia is associated with increased mortality. The reasons for this remain unclear, and the effects of low glucose exposure on vascular endothelial function remain largely unknown. We endeavored to determine the effects of low glucose on endothelial cells and intact human arterioles. Methods and Results—: We exposed human umbilical vein endothelial cells to low glucose conditions in a clinically relevant range (40–70 mg/dL) and found rapid and marked reductions in nitric oxide (NO) bioavailability ( P P P G -Nitroarginine methyl ester. Intact human arterioles exposed to low glucose demonstrated marked endothelial dysfunction, which was prevented by either metformin or TEMPOL. Conclusion—: Our data suggest that moderate low glucose exposure rapidly impairs NO bioavailability and endothelial function in the human endothelium and that pharmacological AMP kinase activation inhibit this effect in an NO-dependent manner.Keywords
This publication has 46 references indexed in Scilit:
- Regulation of Endothelial Function by Mitochondrial Reactive Oxygen SpeciesAntioxidants and Redox Signaling, 2011
- Endothelial nitric oxide synthase negatively regulates hydrogen peroxide-stimulated AMP-activated protein kinase in endothelial cellsProceedings of the National Academy of Sciences, 2009
- Reactive oxygen species and the control of vascular functionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- AMP-Activated Protein Kinase Functionally Phosphorylates Endothelial Nitric Oxide Synthase Ser633Circulation Research, 2009
- How mitochondria produce reactive oxygen speciesBiochemical Journal, 2008
- Bidirectional Actions of Hydrogen Peroxide on Endothelial Nitric-oxide Synthase Phosphorylation and FunctionPublished by Elsevier BV ,2008
- Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 DiabetesNew England Journal of Medicine, 2008
- Effects of Intensive Glucose Lowering in Type 2 DiabetesNew England Journal of Medicine, 2008
- Phosphorylation of LKB1 at Serine 428 by Protein Kinase C-ζ Is Required for Metformin-Enhanced Activation of the AMP-Activated Protein Kinase in Endothelial CellsCirculation, 2008
- Abnormal Glucose Counterregulation after Subcutaneous Insulin in Insulin-Dependent Diabetes MellitusNew England Journal of Medicine, 1984