title: Vascular dysfunction in streptozotocin-induced experimental diabetes strictly depends on insulin deficiency.
abstract: OBJECTIVE
  In previous studies we and others have shown that streptozotocin (STZ)-induced diabetes in rats is associated with vascular oxidative stress and dysfunction. In the present study, we sought to determine whether vascular dysfunction and oxidative stress strictly depend on insulin deficiency.
  
  
  METHODS
  The effects of insulin (2.5 U/day s.c., 2 weeks) therapy on vascular disorders in STZ-induced (60 mg/kg i.v., 8 weeks) diabetes mellitus (type I) were studied in Wistar rats. The contribution of NADPH oxidase to overall oxidative stress was investigated by in vivo (30 mg/kg/day s.c., 4 days) and in vitro treatment with apocynin.
  
  
  RESULTS
  Insulin therapy completely normalized blood glucose, body weight, vascular dysfunction and oxidative stress as well as increased cardiac reactive oxygen and nitrogen species formation in diabetic rats, although diabetes was already established for 6 weeks before insulin therapy was started for the last 2 weeks of the total treatment interval. Apocynin normalized cardiac NADPH oxidase activity, and L-NAME effects suggest a role for uncoupled endothelial nitric oxide synthase in diabetic vascular complications.
  
  
  CONCLUSIONS
  Our findings indicate that STZ-induced diabetes is a model of insulin-dependent diabetes (type 1) and that cardiovascular complications are probably not associated with systemic toxic side effects of STZ.
authors.affiliation: Second Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Oelze
authors.forename: Maike
authors.initials: M
authors.lastname: Knorr
authors.forename: Swenja
authors.initials: S
authors.lastname: Schuhmacher
authors.forename: Tjebo
authors.initials: T
authors.lastname: Heeren
authors.forename: Christian
authors.initials: C
authors.lastname: Otto
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schulz
authors.forename: Kurt
authors.initials: K
authors.lastname: Reifenberg
authors.forename: Philip
authors.initials: P
authors.lastname: Wenzel
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.forename: Andreas
authors.initials: A
authors.lastname: Daiber
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D007328:Insulin / Q000172:deficiency*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019255:NADPH Oxidases / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D000098:Acetophenones; D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; C056165:acetovanillone; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D019331:NG-Nitroarginine Methyl Ester