title: Inhaled aerosolized insulin ameliorates hyperglycemia-induced inflammatory responses in the lungs in an experimental model of acute lung injury.
abstract: BACKGROUND
  Previous studies have shown that patients with diabetes mellitus appear to have a lower prevalence of acute lung injury. We assumed that insulin prescribed to patients with diabetes has an anti-inflammatory property and pulmonary administration of insulin might exert beneficial effects much more than intravenous administration.
  
  
  METHODS
  Twenty-eight mechanically ventilated rabbits underwent lung injury by saline lavage, and then the animals were allocated into a normoglycemia group (NG), a hyperglycemia group (HG), an HG treated with intravenous insulin (HG-VI) group or an HG treated with aerosolized insulin (HG-AI) group with continuous infusion of different fluid solutions and treatments: normal saline, 50% glucose, 50% glucose with intravenous insulin, or 50% glucose with inhaled aerosolized insulin, respectively. After four hours of treatment, the lungs and heart were excised en bloc, and then high-mobility group B1 concentration in bronchoalveolar lavage fluid, interleukin-8 and toll-like receptor 4 mRNA expression in bronchoalveolar lavage fluid cells, and lung myeloperoxidase activity were measured.
  
  
  RESULTS
  Treatment with both aerosolized insulin and intravenous insulin attenuated toll-like receptor 4 mRNA expressions in the bronchoalveolar lavage fluid cells. Interleukin-8 and toll-like receptor 4 mRNA expression was significantly lower in the HG-AI group than in the HG-IV group. The lung myeloperoxidase activity in the normal healthy group showed significantly lower levels compared to the NG group but not different compared to those of the HG, HG-VI and HG-AI groups.
  
  
  CONCLUSIONS
  The results suggest that insulin attenuates inflammatory responses in the lungs augmented by hyperglycemia in acute lung injury and the insulin's efficacy may be better when administered by aerosol.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakazawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Miori
authors.initials: M
authors.lastname: Inoue
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.forename: Koshi
authors.initials: K
authors.lastname: Makita
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000280:Administration, Inhalation; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation
chemical_list: D001786:Blood Glucose; D007328:Insulin