title: Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats.
abstract: OBJECTIVE
  We compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance.
  
  
  METHODS
  Female Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods.
  
  
  RESULTS
  There was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3±0.09, 0.82±0.08; p<0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17±0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3±0.15, 1.11±0.12) was significantly higher than controls (0.56±0.13; p<0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65.
  
  
  CONCLUSIONS
  We conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.
authors: Section of Endocrinology, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA. smurthy@tulane.edu
authors: Subramanyam N
authors: SN
authors: Murthy
authors: Edward A
authors: EA
authors: Pankey
authors: Ajaz A
authors: AA
authors: Banka
authors: Adeleke M
authors: AM
authors: Badejo
authors: Ryan
authors: R
authors: Wekerle
authors: Vaitaitis
authors: V
authors: Vilija
authors: Reza
authors: R
authors: Izadpanah
authors: Philip J
authors: PJ
authors: Kadowitz
authors: Vivian A
authors: VA
authors: Fonseca
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D006965:Hyperplasia; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069057:Insulin Detemir; D007333:Insulin Resistance; D007336:Insulin, Isophane / Q000627:therapeutic use; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D017539:Tunica Intima / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat