title: PPAR gamma agonist normalizes glomerular filtration rate, tissue levels of homocysteine, and attenuates endothelial-myocyte uncoupling in alloxan induced diabetic mice.
abstract: BACKGROUND
  Homocysteine (Hcy) is an independent cardiovascular risk factor; however, in diabetes, the role of tissue Hcy leading to cardiac dysfunction is unclear.
  
  
  OBJECTIVE
  To determine whether tissue Hcy caused endothelial-myocyte uncoupling and ventricular dysfunction in diabetes.
  
  
  METHODS
  Diabetes was created in C57BL/6J male mice by injecting 65 mg/kg alloxan. To reverse diabetic complications, ciglitazone (CZ) was administered in the drinking water. Plasma glucose, Hcy, left ventricular (LV) tissue levels of Hcy and nitric oxide (NO) were measured. Glomerular filtration rate (GFR) was measured by inulin-FITC. Endothelial-myocyte coupling was measured in cardiac rings. In vivo diastolic relaxation and LV diameters were measured by a Millar catheter in LV and by M-mode echocardiography, respectively.
  
  
  RESULTS
  Plasma glucose, GFR and LV tissue Hcy were increased in diabetic mice and were normalized after CZ treatment; whereas, elevated plasma Hcy level remained unchanged with or without CZ treatment. NO levels in the LV were found inversely related to tissue Hcy levels. Attenuated endothelial-myocyte function in diabetic mice was ameliorated by CZ treatment. Cardiac relaxation, the ratio of LV wall thickness to LV diameter was decreased in diabetes, and normalized after CZ treatment.
  
  
  CONCLUSIONS
  CZ normalized LV tissue levels of Hcy and ameliorated endothelial-myocyte coupling; therefore, specifically suggest the association of LV tissue Hcy levels with impair endothelial-myocyte function in diabetes.
authors.affiliation: Department of Physiology, Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Rodriguez
authors.forename: Utpal
authors.initials: U
authors.lastname: Sen
authors.forename: Neetu
authors.initials: N
authors.lastname: Tyagi
authors.forename: Munish
authors.initials: M
authors.lastname: Kumar
authors.forename: Gene
authors.initials: G
authors.lastname: Carneal
authors.forename: Deep
authors.initials: D
authors.lastname: Aggrawal
authors.forename: Justin
authors.initials: J
authors.lastname: Newsome
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000496:Alloxan; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006710:Homocysteine / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D006710:Homocysteine; D000496:Alloxan; C039671:ciglitazone