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Open AccessJournal ArticleDOI

Vitamin C Further Improves the Protective Effect of Glucagon-Like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress, Inflammation, and Endothelial Dysfunction in Type 1 Diabetes

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TLDR
Vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes.
Abstract
OBJECTIVE To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes. RESEARCH DESIGN AND METHODS A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. RESULTS At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. CONCLUSIONS This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.

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Citations
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Journal ArticleDOI

Vitamin C: the known and the unknown and Goldilocks.

TL;DR: Vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited are reviewed; questions about the vitamin that remain to be answered are raised; and lines of investigations that are likely to be fruitful are explored.
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Glycemic Variability and Oxidative Stress: A Link between Diabetes and Cardiovascular Disease?

TL;DR: It is suggested that management of glycemic variability may reduce cardiovascular disease in patients with diabetes; however, clinical studies have shown conflicting results.
Book ChapterDOI

Dietary Vitamin C in Human Health.

TL;DR: There is no evidence that vitamin C supplementation impacts the risks for all-cause mortality, impaired cognitive performance, reduced quality of life, the development of eye diseases, infections, cardiovascular disease, and cancers.
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Glucose variability, HbA1c and microvascular complications.

TL;DR: It is concluded that randomized prospective follow-up trials could possibly help estimate whether short-term glucose variability should be considered as an independent risk factor for microvascular complications in diabetes.
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ERK2 Mediates Metabolic Stress Response to Regulate Cell Fate

TL;DR: It is shown that under low-glucose conditions, cells initiate adaptation followed by apoptosis responses using PERK/Akt and MEK1/ERK2 signaling, respectively, which reveal promising targets to protect cells or tissues from metabolic stress.
References
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Journal ArticleDOI

Oxidative stress and diabetic complications

TL;DR: Athrosclerosis and cardiomyopathy in type 2 diabetes are caused in part by pathway-selective insulin resistance, which increases mitochondrial ROS production from free fatty acids and by inactivation of antiatherosclerosis enzymes by ROS.
Journal ArticleDOI

Diabetes and cardiovascular disease.

TL;DR: The impact of diabetes on CVD is examined, and LDL cholesterol and albuminuria should be the targets of preventive strategies, and promising new areas such as cytokines, growth factor, and the role of infection should be further explored.
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The Value of Cardiovascular Autonomic Function Tests: 10 Years Experience in Diabetes

TL;DR: Comparison between a single test (heart rate response to deep breathing) and the full battery in 360 subjects showed that one test alone does not distinguish the degree or severity of autonomic damage.
Journal ArticleDOI

Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells: The Role of Protein Kinase C and NAD(P)H-Oxidase Activation

TL;DR: The study shows that the exposure of endothelial cells to both stable and intermittent high glucose stimulates reactive oxygen species overproduction also through PKC-dependent activation of NAD(P)H oxidase, leading to increased cellular apoptosis, suggesting that glucose fluctuations may also be involved in the development of vascular injury in diabetes.
Journal ArticleDOI

Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia.

TL;DR: It is demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hyp glucosecemia, much of which occurred at home during waking hours.
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