title: Pulsatile Hyperglycaemia Induces Vascular Oxidative Stress and GLUT 1 Expression More Potently than Sustained Hyperglycaemia in Rats on High Fat Diet.
abstract: BACKGROUND
  Pulsatile hyperglycaemia resulting in oxidative stress may play an important role in the development of macrovascular complications. We investigated the effects of sustained vs. pulsatile hyperglycaemia in insulin resistant rats on markers of oxidative stress, enzyme expression and glucose metabolism in liver and aorta. We hypothesized that liver's ability to regulate the glucose homeostasis under varying states of hyperglycaemia may indirectly affect oxidative stress status in aorta despite the amount of glucose challenged with.
  
  
  METHODS
  Animals were infused with sustained high (SHG), low (SLG), pulsatile (PLG) glucose or saline (VEH) for 96 h. Oxidative stress status and key regulators of glucose metabolism in liver and aorta were investigated.
  
  
  RESULTS
  Similar response in plasma lipid oxidation was observed in PLG as in SHG. Likewise, in aorta, PLG and SHG displayed increased expression of glucose transporter 1 (GLUT1), gp-91PHOX and super oxide dismutase (SOD), while only the PLG group showed increased accumulation of oxidative stress and oxidised low density lipoprotein (oxLDL) in aorta.
  
  
  CONCLUSIONS
  Pulsatile hyperglycaemia induced relatively higher levels of oxidative stress systemically and in aorta in particular than overt sustained hyperglycaemia thus supporting the clinical observations that pulsatile hyperglycaemia is an independent risk factor for diabetes related macrovascular complications.
authors.affiliation: Department of Experimental Animal Models, Section of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Diabetes Pharmacology, Global Research, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Günaj
authors.initials: G
authors.lastname: Rakipovski
authors.affiliation: Department of Experimental Animal Models, Section of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.affiliation: Department of Diabetes Pharmacology, Global Research, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Raun
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000209:etiology / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger