ArticleThe Journal of clinical investigation1996
Glucose-induced phosphorylation of the insulin receptor. Functional effects and characterization of phosphorylation sites.
Article in The Journal of clinical investigation, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 74 citations in OpenAlex.
- High Glucose Impairs Insulin Signaling in the Glomerulus: An In Vitro and Ex Vivo Approach.PloS one · 2016Article
- Inhibition of insulin signaling in endothelial cells by protein kinase C-induced phosphorylation of p85 subunit of phosphatidylinositol 3-kinase (PI3K).The Journal of biological chemistry · 2012Article
- Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport.Nature medicine · 2011Article
- In vivo activation of ROCK1 by insulin is impaired in skeletal muscle of humans with type 2 diabetes.American journal of physiology. Endocrinology and metabolism · 2011Article
- Glycogen synthase kinase 3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1.The Journal of endocrinology · 2010Article
- Insulin-like growth factor-I stimulates Shc-dependent phosphatidylinositol 3-kinase activation via Grb2-associated p85 in vascular smooth muscle cells.The Journal of biological chemistry · 2008Article
- Chronic hyperglycaemia promotes lipogenesis and triacylglycerol accumulation in human skeletal muscle cells.Diabetologia · 2004Article
- Selective impairment of insulin signalling in the hypothalamus of obese Zucker rats.Diabetologia · 2003Article
- Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.The Journal of clinical investigation · 1999 · on this mapArticle
- Elevated D-glucose induces insulin insensitivity in human umbilical endothelial cells isolated from gestational diabetic pregnancies.The Journal of physiology · 1998Article
- Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk.The Journal of clinical investigation · 1997Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Elevated glucose concentrations have been reported to inhibit insulin receptor kinase activity. We studied the effects of high glucose on insulin action in Rat1 fibroblasts transfected with wild-type human insulin receptor (HIRcB) and a truncated receptor lacking the COOH-terminal 43 amino acids (delta CT). In both cell lines, 25 mM glucose impaired receptor and insulin receptor substrate-1 phosphorylation by 34%, but IGF-1 receptor phosphorylation was unaffected. Phosphatidylinositol 3-kinase activity and bromodeoxyuridine uptake were decreased by 85 and 35%, respectively. This was reversed by coincubation with a protein kinase C (PKC) inhibitor or microinjection of a PKC inhibitor peptide. Phosphopeptide mapping revealed that high glucose or PMA led to serine/threonine phosphorylation of similar peptides. Inhibition of the microtubule-associated protein (MAP) kinase cascade by the MAP kinase kinase inhibitor PD98059 did not reverse the impaired phosphorylation. We conclude that high glucose inhibits insulin action by inducing serine phosphorylation through a PKC-mediated mechanism at the level of the receptor at sites proximal to the COOH-terminal 43 amino acids. This effect is independent of activation of the MAP kinase cascade. Proportionately, the impairment of insulin receptor substrate-1 tyrosine phosphorylation is greater than that of the insulin receptor resulting in attenuated phosphatidylinositol 3-kinase activation and mitogenic signaling.
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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.