title: Block by nitrate tolerance of meal-induced insulin sensitization in conscious rabbits.
abstract: OBJECTIVE
  Hemodynamic nitrate tolerance has been shown to result in an insulin-resistant state. We studied whether nitrate tolerance induced by a 7-day continuous exposure to transdermal nitroglycerin influenced the meal-induced insulin sensitization phenomenon in rabbits.
  
  
  METHODS
  Changes in insulin sensitivity in response to feeding in conscious rabbits were determined by rapid insulin sensitivity test, in both nitrate-tolerant and nitrate-intolerant animals. In a separate series of experiments with anesthetized rabbits with or without nitrate tolerance, the hyperinsulinemic euglycemic glucose clamping methods was used to study the effect of intraportal infusion of cholecystokinin (CCK) on whole-body insulin sensitivity.
  
  
  RESULTS
  Rabbits with normal feeding exhibited a 46 ± 6% increase in insulin sensitivity as compared with their matching fasting controls. A 7-day period of treatment with patches releasing 0.07 mg of nitroglycerin per hour yielded nitrate tolerance and a state of insulin resistance and no increase in insulin sensitivity in response to food. Intraportal infusion of CCK8 (0.3-3.0 μg/kg over 20 minutes) resulted in a dose-dependent increase in insulin sensitivity in normal but not in nitrate-tolerant, fasted anesthetized animals.
  
  
  CONCLUSIONS
  Nitrate tolerance blocks both the meal-induced insulin sensitization phenomenon and the insulin-sensitizing effect of intraportal CCK.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, University of Debrecen, Debrecen, Hungary.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bajza
authors.forename: József
authors.initials: J
authors.lastname: Németh
authors.forename: Barna
authors.initials: B
authors.lastname: Peitl
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szilvássy
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology*; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology; D015309:Glucose Clamp Technique; D006339:Heart Rate / Q000187:drug effects; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012844:Sincalide / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D005996:Nitroglycerin; D006152:Cyclic GMP; D012844:Sincalide