title: Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK) phosphorylation in renal and vascular dysfunction.
abstract: BACKGROUND
  In the present study we tested the hypothesis that progression of streptozotocin (STZ)-induced diabetes (14-days to 28-days) would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK) phosphorylation in kidneys and thoracic aorta.
  
  
  METHODS
  Male Sprague Dawley rats (350-400 g) were randomized into three groups: sham (N = 6), 14-days diabetic (N = 6) and 28-days diabetic rats (N = 6). Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V.) on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat.
  
  
  RESULTS
  The diabetic rats lost body weight at both 14-days (-10%) and 28-days (-13%) more significantly as compared to sham (+10%) group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS), prepro endothelin-1 (preproET-1) and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group.
  
  
  CONCLUSIONS
  The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy North Dakota State University, Fargo, ND 58105, USA. Hongmei.chen@ndsu.edu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Chen
authors.forename: Sachin
authors.initials: S
authors.lastname: Brahmbhatt
authors.forename: Akanksha
authors.initials: A
authors.lastname: Gupta
authors.forename: Avadhesh C
authors.initials: AC
authors.lastname: Sharma
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D002319:Cardiovascular System / Q000737:chemistry / Q000503:physiopathology*; D002339:Carotid Arteries / Q000503:physiopathology; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000503:physiopathology*; D007672:Kidney Cortex / Q000098:blood supply / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D019332:Endothelin-1; D003404:Creatinine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases