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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Arteriosclerosis, Cells, Cultured, Coronary Vessels, Diabetes Complications, Dose-Response Relationship, Drug, Endothelium, Vascular, Enzyme Activation, Glucosamine, Glucose, Glycosylation, Humans, Insulin, Insulin Antagonists, Matrix Metalloproteinases, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Phosphorylation, Proteins, Signal Transduction, Tissue Inhibitor of Metalloproteinase-3.
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Is insulin-dependent activation of endothelial nitric oxide synthase impaired by O-linked glycosylation modification of signaling proteins in human coronary endothelial cells? Context: 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. 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.
assistant
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. Final Decision: yes