Insulin attenuates endotoxin-induced acute lung injury in conscious rats.
OBJECTIVE
To investigate the effects of insulin on the acute lung injury induced by lipopolysaccharide using a conscious rat model.


METHODS
Prospective, randomized, controlled animal study.


METHODS
University research laboratory.


METHODS
A total of 190 adult male Sprague-Dawley rats weighing 250-300 g.


METHODS
Endotoxemia was induced by intravenous infusion of lipopolysaccharide. Lipopolysaccharide at various doses (0, 1, 5, 10, 20, and 30 mg/kg, n=10 for each dose) was administered intravenously in 20 mins. Insulin infusion at doses of 0.5, 1, and 5 microU/kg/min was given 5 mins before lipopolysaccharide administration. Plasma glucose was clamped at 90-110 mg/dL by infusion of 10-80% glucose solution. Insulin and glucose infusion (0.01 mL/min) was started 5 mins before lipopolysaccharide and continued for 120 mins. The rats received a total of 60, 120, and 600 microU/kg insulin as well as 0.12, 0.36, and 0.96 g of glucose in respective groups. The animals were then observed for 4 hrs.


RESULTS
The extent of acute lung injury was evaluated by lung weight/body weight ratio, lung weight gain, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. We also measured plasma nitrate/nitrite and methyl guanidine. In addition, histopathologic changes of the lung were examined. Lipopolysaccharide caused systemic hypotension and severe acute lung injury with increases in plasma nitrate/nitrite and methyl guanidine. Pretreatment with insulin infusion at doses of 0.5, 1, and 5 microU/kg/min mitigated or prevented systemic hypotension and the development of acute lung injury, depending on the dose. Insulin also attenuated the lipopolysaccharide-induced increases in nitrate/nitrite and methyl guanidine.


CONCLUSIONS
Insulin is effective in reducing or preventing the lipopolysaccharide-induced increases in plasma nitrate/nitrite and methyl guanidine and the occurrence of acute lung injury.
Chen
Hsing I
HI
Institute of Medical Science, Tzu Chi University, Hualien, and Department of Chest Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Yeh
Diana Y
DY
Liou
Huey-Ling
HL
Kao
Shang-Jyh
SJ
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007022:Hypotension / Q000517:prevention & control; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
D007004:Hypoglycemic Agents; D007328:Insulin; D008070:Lipopolysaccharides; D009569:Nitric Oxide