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AdvisorRizk, Nasser
AuthorBushra, Sumbul
Available date2015-12-03T08:57:48Z
Publication Date2015-06
URIhttp://hdl.handle.net/10576/3900
AbstractDiabetic retinopathy (DR) a major consequence of diabetes is considered the leading cause of vision loss and blindness worldwide among working adults. Endothelial dysfunction expediting imbalance in vascular homeostasis, is one of the primary manifestation leading to the pathogenesis of DR. NO a major vasodilator involved in the regulation of vascular homeostasis is reported to be released by insulin dependent PI3K/ Akt signaling pathway. Endothelial dysfunction impairs ocular hemodynamics by reducing the bioavailability of NO and increasing the production of reactive oxygen species (ROS) and may be responsible for the pathogenesis of vascular dysfunction in retinopathy. In the current study in order to examine the effect of insulin on NO production, HRECs cells were cultured and grown in high glucose (30mM) and normal (5mM) glucose for 24 hours. Subsequently, the cells were treated with 100nM insulin for 10 minutes, 1, 2, and 4 hours. The various parameters of PI3K/ Akt signaling pathway were analyzed. This study demonstrated that Hyperglycemia causes an increase in ROS/oxidative stress and apoptosis, while insulin promotes a significant decrease in ROS and apoptosis, eNOS mediated NO production increases with hyperglycemia but remarkably reduced with insulin treatment after 1hour, 2 hours and 4 hours. This may suggest that insulin could counteract the hyperglycemic effect on AKT/PI3 kinase which mediates NO production and VEGF-A, with decreased adhesion molecules such as p-selectin that is involved in barrier disorder of retinal endothelial cells. In summary, insulin could counteract the deleterious effects of hyperglycemia on retinal endothelial cells via various molecular approach including oxidative stress, apoptosis, NO, and adhesion molecules.
Languageen
SubjectEndothelial dysfunction
SubjectRetinopathy
SubjectInsulin treatment
TitleASSOCIATION BETWEEN INSULIN RESISTANCE AND NITRIC OXIDE IN HUMAN RETINAL MICROVASCULAR ENDOTHELIAL CELLS IN VITRO
TypeMaster Thesis
DepartmentHealth Sciences


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