The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Insulin-Dependent Activation of Endothelial Nitric Oxide Synthase Is Impaired by O-Linked Glycosylation Modification of Signaling Proteins in Human Coronary Endothelial Cells
Open accessAbstract
Background — Hyperglycemia impairs functional properties of cytosolic and nuclear proteins via O-linked glycosylation modification (O-GlcNAcylation). We studied the effects of O-GlcNAcylation on insulin signaling in human coronary artery endothelial cells. Methods and Results — O-GlcNAcylation impaired the metabolic branch of insulin signaling, ie, insulin receptor (IR) activation of the IR substrate (IRS)/phosphatidylinositol 3-kinase (PI3-K)/Akt, whereas it enhanced the mitogenic branch, ie, ERK-1/2 and p38 (mitogen-activated protein kinase). Both in vivo and in vitro phosphorylation of endothelial nitric oxide synthase (eNOS) by Akt were reduced by hyperglycemia and hexosamine activation. Insulin-induced eNOS activity in vivo was reduced by hyperglycemia and hexosamine activation, which was coupled to increased activation and expression of matrix metalloproteinase-2 and -9; these phenomena were reversed by inhibition of the hexosamine pathway. Finally, carotid plaques from type 2 diabetic patients showed increased endothelial O-GlcNAcylation with respect to nondiabetics. Conclusions — Our data show that hyperglycemia, through the hexosamine pathway, impairs activation of the IR/IRS/PI3-K/Akt pathway, resulting in deregulation of eNOS activity.
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Cites
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Cited by
The Pathobiology of Diabetic Complications
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Cycling of O-linked β-N-acetylglucosamine on nucleocytoplasmic proteins
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Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
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Cardiovascular Actions of Insulin
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Metadata
- Authors
- Federici, M., Menghini, R., Mauriello, A., Hribal, M. L., Ferrelli, F., Lauro, D., Sbraccia, P., Spagnoli, L. G., Sesti, G., & Lauro, R.
- Venue
- Circulation
- Published
- 2002-07-23
- Volume
- 106
- Issue
- 4
- Pages
- 466-472
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2162431165
- Cited by
- 373
- References
- 36
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Federici, M., Menghini, R., Mauriello, A., Hribal, M. L., Ferrelli, F., Lauro, D., Sbraccia, P., Spagnoli, L. G., Sesti, G., & Lauro, R. (2002). Insulin-Dependent Activation of Endothelial Nitric Oxide Synthase Is Impaired by O-Linked Glycosylation Modification of Signaling Proteins in Human Coronary Endothelial Cells. Circulation. https://doi.org/10.1161/01.cir.0000023043.02648.51
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