الفهرس 
Diabetes Mellitus (DM)
Diabetic NephropathyOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus is a worldwide metabolic health burden characterized by persistent chronic hyperglycemia resulting in multiple complications. It may be caused by deficient insulin secretion, insulin action, or both. One of diabetic complications is Diabetic nephropathy that is a leading cause of chronic kidney disease worldwide. Diabetes is responsible for 30-40% of all end-stage renal disease (ESRD) cases. Other complications include retinopathy, neuropathy and vasculopathy
Proteinuria is the hallmark of diabetic nephropathy (DN), usually worsens with progression of diabetic kidney disease. It is characterized by diminishing glomerular filtration rate and other glomerular structural changes, including thickening of the basement membranes and mesangial sclerosis. Several mechanisms implicated in progression of Diabetic kidney disease (DKD) including buildup of advanced glycation end products, polyol pathway, hexosamine pathway, protein kinase C (PKC) activation and glomerular vascular changes together with over expression of inflammatory cytokines.
Mitochondria are energy producing factories that are responsible for ATP production through oxidative phosphorylation, production of reactive oxygen species (ROS), fusion/fission events and regulation of apoptosis. Diabetic nephropathy affects cellular oxidative balance through overproduction of ROS together with increased rate of mitophagy.Optic Atrophy 1 (OPA1) is an inner mitochondrial membrane protein responsible for mitochondrial fusion with stabilization of mitochondrial cristae to protect against mitochondrial dysfunction. In Diabetic Nephropathy, down-regulation of OPA1 in response to ROS result in abolished mitochondrial fusion, release of cytochrome c ending in mitochondrial shortening and fragmentation.
Dynamin-related protein 1 (Drp1) is an outer mitochondrial membrane protein responsible for mitochondrial fission. In Diabetic Nephropathy, over-expression of DRP1 result in induction of GTP hydrolysis-mediated membrane constriction, Pumping of Ca2+ signals from the endoplasmic reticulum, cytochrome c release with premature autophagy. Hyperglycemic induced ROS result in consumption of antioxidant especially reduced glutathione. In chronic persistent hyperglycemia, cellular exhaustion of antioxidant reserve causing its depletion making the oxidative processes irreversible with evident cell injury.