title: Losartan affects glomerular AKT and mTOR phosphorylation in an experimental model of type 1 diabetic nephropathy.
abstract: The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.
authors: Department of Nephrology, University of Crete, Greece. vasiliki.mavroeidi@gmail.com
authors: Vasiliki
authors: V
authors: Mavroeidi
authors: Ioannis
authors: I
authors: Petrakis
authors: Kostas
authors: K
authors: Stylianou
authors: Theodora
authors: T
authors: Katsarou
authors: Konstantinos
authors: K
authors: Giannakakis
authors: Kostas
authors: K
authors: Perakis
authors: Eleftheria
authors: E
authors: Vardaki
authors: Spyridon
authors: S
authors: Stratigis
authors: Emmanuel
authors: E
authors: Ganotakis
authors: Stathis
authors: S
authors: Papavasiliou
authors: Eugenios
authors: E
authors: Daphnis
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D019808:Losartan
keywords: AKT; diabetic nephropathy; losartan; mTOR; podocytes; type 1 diabetes