title: Nitric oxide differentially affects ERK and Akt in type 1 and type 2 diabetic rats.
abstract: BACKGROUND
  We have shown that nitric oxide (NO) is more effective at inhibiting neointimal hyperplasia in type 2 diabetic rats than in nondiabetic rats, but is not effective in type 1 diabetic rats. Insulin signaling is mediated by the ERK and Akt pathways, and thus we hypothesized that NO differentially affects ERK and Akt activity in type 1 versus type 2 diabetic rats.
  
  
  METHODS
  To investigate this hypothesis, we induced type 2 diabetes in Zucker diabetic fatty (ZDF) rats by feeding them Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60 mg/kg). The carotid artery injury model was performed. Groups included injury and injury + PROLI/NO (20 mg/kg) (n = 6/group).
  
  
  RESULTS
  Three days following injury, all animal models exhibited an increase in pERK levels. Whereas NO reduced pERK levels in LZ and STZ rats, NO had no effect on pERK levels in ZDF rats. Following a similar pattern, NO reduced pAkt levels in LZ and STZ rats but increased pAkt levels in ZDF rats. Fourteen days following injury, NO increased total pERK levels throughout the arterial wall in both the STZ and ZDF rats. These changes were greatest in the adventitia. Interestingly, whereas NO decreased total pAkt levels in LZ and STZ rats, NO increased pAkt levels in ZDF rats. Evaluation of the pERK:pAkt ratio revealed that NO increased this ratio in LZ and STZ rats but decreased the ratio in ZDF rats.
  
  
  CONCLUSIONS
  We report that NO differentially affects the expression of pERK and pAkt in type 1 versus type 2 diabetic rats. Given that NO is more effective at inhibiting neointimal hyperplasia in type 2 diabetic animals, the pERK:pAkt ratio may be the best surrogate to predict efficacy.
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Rodriguez
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Emond
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Vinit N
authors.initials: VN
authors.lastname: Varu
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sadaf S
authors.initials: SS
authors.lastname: Ahanchi
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.|Jesse Brown VA Medical Center, Chicago, Illinois.
authors.forename: Janet
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Division of Vascular Surgery and Institute for BioNanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.|Jesse Brown VA Medical Center, Chicago, Illinois.
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D006965:Hyperplasia; D008297:Male; D058426:Neointima / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013311:Streptozocin / Q000009:adverse effects
chemical_list: D009569:Nitric Oxide; D013311:Streptozocin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Akt; ERK; Metabolic environment; Neointimal hyperplasia; Nitric oxide; Type 1 diabetes; Type 2 diabetes