title: Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance.
abstract: Kinins are vasoactive and pro-inflammatory peptides whose biological effects are mediated by two GPCRs, named B1 and B2 receptors. While the B2 receptor plays a protective role in the cardiovascular system via the activation of endothelial NOS, the B1 receptor is associated with vascular inflammation, insulin resistance and diabetic complications. Because the B1 receptor is a potent activator of the inducible form of NOS (iNOS), this study has addressed the role of iNOS in the deleterious effects of B1 receptors in insulin resistance.
  
  
  
  Male Sprague-Dawley rats (50-75 g) had free access to a drinking solution containing 10% d-glucose or tap water (control) for 9 weeks. During the last week, a selective iNOS inhibitor (1400W, 1 mg·kg(-1) twice daily) or its vehicle was administered s.c.
  
  
  
  Prolonged glucose treatment caused insulin resistance and several hallmarks of type 2 diabetes. Whereas the treatment with 1400W had no impact on the elevated systolic blood pressure and leptin levels in glucose-fed rats, it significantly reversed or attenuated hyperglycaemia, hyperinsulinaemia, insulin resistance (HOMA index), body weight gain, peroxynitrite formation (nitrotyrosine expression) and the up-regulation of biomarkers of inflammation (B1 receptor, carboxypeptidase M, iNOS and IL-1β) in renal cortex and aorta and to some extent in the liver.
  
  
  
  Pharmacological blockade of iNOS prevents the formation of peroxynitrite, which amplifies the pro-inflammatory effects of B1 receptors through a positive feedback mechanism. Hence, targeting iNOS can prevent the deleterious effects of B1 receptors in insulin resistance and peripheral inflammation.
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haddad
authors.affiliation: Department of Molecular and Integrative Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
authors.forename: Réjean
authors.initials: R
authors.lastname: Couture
mesh_terms: D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007333:Insulin Resistance; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000578:Amidines; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D043783:Receptor, Bradykinin B1; D052247:Nitric Oxide Synthase Type II