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Cited by 769

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells

Open access
Quagliaro, Lisa, Piconi, Ludovica, Assaloni, Roberta, Martinelli, Lucia, Motz, Enrico, Ceriello, Antonio·2003·Diabetes

Abstract

The effects of intermittent and constant high glucose in the formation of nitrotyrosine and 8-hydroxydeoxyguanosine (markers of oxidative stress), as well as the possible linkage between oxidative stress and apoptosis in endothelial cells, have been evaluated. Stable high glucose increased nitrotyrosine, 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis levels. However, these effects were more pronounced in intermittent high glucose. Protein kinase C (PKC) was elevated in both such conditions, particularly in intermittent glucose. The adding of the PKC inhibitors bisindolylmaleimide-I and LY379196, a specific inhibitor of PKC-β isoforms, normalized nitrotyrosine and reduced 8-OHdG concentration and cell apoptosis in both stable and intermittent high glucose. Similar results were obtained with the MnSOD mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride that normalized nitrotyrosine, 8-OHdG, and apoptosis and inhibited PKC activation. NAD(P)H oxidase was also measured. NAD(P)H oxidase components p47phox, p67phox, and p22phox was overexpressed during both stable and intermittent high glucose. PKC inhibition and MnSOD mimetic normalized this phenomenon. In conclusion, our 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. Our data suggest that glucose fluctuations may also be involved in the development of vascular injury in diabetes.

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Metadata

Authors
Quagliaro, L., Piconi, L., Assaloni, R., Martinelli, L., Motz, E., & Ceriello, A.
Venue
Diabetes
Published
2003-11-01
Volume
52
Issue
11
Pages
2795-2804
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2098036900
Cited by
769
References
35
FWCI
12.85
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells. https://app.cochat.ai/papers/10.2337/diabetes.52.11.2795
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Quagliaro, L., Piconi, L., Assaloni, R., Martinelli, L., Motz, E., & Ceriello, A. (2003). Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells. Diabetes. https://doi.org/10.2337/diabetes.52.11.2795

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