Abstract
Insulin resistance is associated with deficits in glucose metabolism. We tested whether the vascular and renal responses to insulin might contribute to insulin resistance. Generation of endothelial-derived vasodilator nitric oxide (NO), estimated after a 2-h period of insulin stimulation, was inhibited in the presence of high glucose. Immunoprecipitations indicated that insulin-induced endothelial signal transduction was mediated through an immediate complex formation of insulin receptor substrate (IRS) with phosphatidylinositol 3-kinase, which caused serine phosphorylation of a protein complex that was comprised of Akt kinase and endothelial NO synthase. The enzymatic complexes did not form when the endothelial insulin stimulation occurred in the presence of high glucose concentrations. By contrast, neither epithelial signal transduction nor sodium transport in renal epithelial cells was affected by high glucose. Hence, glucose does not appear to modulate either the epithelial IRS cascade or renal sodium retention. Dysfunction of the endothelial IRS cascade and NO generation, which suppresses efficient delivery of nutrients, may further exacerbate the metabolic syndrome of insulin resistance.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: American journal of physiology. Endocrinology and metabolism
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.