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Cited by 323

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells

Open access
Ido, Yasuo, Carling, David, Ruderman, Neil·2002·Diabetes

Abstract

Apoptosis has been observed in vascular cells, nerve, and myocardium of diabetic humans and experimental animals, although whether it contributes to or is a marker of complications in these tissues is unclear. Previous studies have shown that incubation of human umbilical vein endothelial cells (HUVECs) with 30 vs. 5 mmol/l glucose for 72 h causes a significant increase in apoptosis, possibly related to an increase in oxidative stress. We report here that this increase in apoptosis (assessed morphologically by TdT-mediated dUTP nick- end labeling staining) is preceded (24 h of incubation) by inhibition of fatty acid oxidation, by increases in diacylglycerol synthesis, the concentration of malonyl CoA, and caspase-3 activity, and by decreases in mitochondrial membrane potential and cellular ATP content. In addition, the phosphorylation of Akt in the presence of 150 μU/ml insulin was impaired. No increases in ceramide content or its de novo synthesis were observed. AMP-activated protein kinase (AMPK) activity was not diminished; however, incubation with the AMPK activator 5-aminoimidazole-4-carboxamide-riboside increased AMPK activity twofold and completely prevented all of these changes. Likewise, expression of a constitutively active AMPK in HUVEC prevented the increase in caspase-3 activity. The results indicate that alterations in fatty-acid metabolism, impaired Akt activation by insulin, and increased caspase-3 activity precede visible evidence of apoptosis in HUVEC incubated in a hyperglycemic medium. They also suggest that AMPK could play an important role in protecting the endothelial cell against the adverse effects of sustained hyperglycemia.

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Metadata

Authors
Ido, Y., Carling, D., & Ruderman, N.
Venue
Diabetes
Published
2002-01-01
Volume
51
Issue
1
Pages
159-167
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W2096979086
Cited by
323
References
48
FWCI
5.94
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells. https://app.cochat.ai/papers/10.2337/diabetes.51.1.159
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Ido, Y., Carling, D., & Ruderman, N. (2002). Hyperglycemia-Induced Apoptosis in Human Umbilical Vein Endothelial Cells. Diabetes. https://doi.org/10.2337/diabetes.51.1.159

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