ArticleThe Journal of biological chemistry2012
Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Resveratrol Impairs Insulin Signaling in Hepatic Cells via Activation of PKC and PTP1B Pathways.International journal of molecular sciences · 2025Article
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?Physiological reports · 2024Review
- Olive Oil's Attenuating Effects on Lipotoxicity.Advances in experimental medicine and biology · 2024Review
- Phosphorylation at tyrosine 317 and 508 are crucial for PIK3CA/p110α to promote CRC tumorigenesis.Cell & bioscience · 2023Article
- Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.Brain : a journal of neurology · 2023Article
- Endothelial Cells Induced Progenitors Into Brown Fat to Reduce Atherosclerosis.Circulation research · 2022Article
- Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.Pflugers Archiv : European journal of physiology · 2022Review
- Insulin's actions on vascular tissues: Physiological effects and pathophysiological contributions to vascular complications of diabetes.Molecular metabolism · 2021Review
- The transcriptional coregulator CITED2 suppresses expression of IRS-2 and impairs insulin signaling in endothelial cells.American journal of physiology. Endocrinology and metabolism · 2021Article
- Potential Roles of Endoplasmic Reticulum Stress and Cellular Proteins Implicated in Diabesity.Oxidative medicine and cellular longevity · 2021Review
- The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases.Biomedicines · 2020Review
- Phlorizin Exerts Direct Protective Effects on Palmitic Acid (PA)-Induced Endothelial Dysfunction by Activating the PI3K/AKT/eNOS Signaling Pathway and Increasing the Levels of Nitric Oxide (NO).Medical science monitor basic research · 2018Article
- Diabetic Microvascular Disease: An Endocrine Society Scientific Statement.The Journal of clinical endocrinology and metabolism · 2017Review
- Safflor yellow B reduces hypoxia-mediated vasoconstriction by regulating endothelial micro ribonucleic acid/nitric oxide synthase signaling.Oncotarget · 2017Article
- Regulation of Macrophage Apoptosis and Atherosclerosis by Lipid-Induced PKCδ Isoform Activation.Circulation research · 2017Article
- Overexpressing IRS1 in Endothelial Cells Enhances Angioblast Differentiation and Wound Healing in Diabetes and Insulin Resistance.Diabetes · 2016Article
- Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture.Diabetes · 2016Article
- PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts.The Journal of clinical investigation · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The regulation of endothelial function by insulin is consistently abnormal in insulin-resistant states and diabetes. Protein kinase C (PKC) activation has been reported to inhibit insulin signaling selectively in endothelial cells via the insulin receptor substrate/PI3K/Akt pathway to reduce the activation of endothelial nitric-oxide synthase (eNOS). In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin's activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. In addition, PKC activation, by general activator and specifically by angiotensin II, increased the phosphorylation of p85/PI3K, which decreases its association with IRS1 and activation. Thr-86 of p85/PI3K was identified to be phosphorylated by PKC activation and confirmed to affect IRS1-mediated activation of Akt/eNOS by insulin and VEGF using a deletion mutant of the Thr-86 region of p85/PI3K. Thus, PKC and angiotensin-induced phosphorylation of Thr-86 of p85/PI3K may partially inhibit the activation of PI3K/eNOS by multiple cytokines and contribute to endothelial dysfunction in metabolic disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.