Lack of a protective effect of insulin on three reperfusion-liver injury models in rats and mice.
Our objective was to investigate the potential protective effects of insulin on the liver injury induced in three ischemia and reperfusion (I/R) models.


METHODS
Three I/R models were used: (1) I/R of the liver was produced in isolated, perfused rat livers; (2) in in situ I/R of the liver in rats, ischemia was induced by clamping off the hepatic artery and portal vein for 40 minutes, the flow then restored, and the liver reperfused for 90 minutes; (3) in in situ I/R of the liver in mice, ischemia was induced by clamping off the hepatic artery for 15 minutes, the flow then restored, and the liver reperfused for 45 minutes. In all three cases, blood samples collected before ischemia and after reperfusion were analyzed for sGOT. Plasma nitrate/nitrite, hydroxyl radicals, and tumor necrosis factor were also measured. In each model, a dose of insulin sufficient to induce euglycemia was administered to assess its protective effect on liver injury and inflammation.


RESULTS
These I/R protocols resulted in a significant increase in sGOT and in three inflammatory parameters; nitric oxide, hydroxyl radicals, and tumor necrosis factor. Pretreatment with insulin did not attenuate the liver injury in any of the three I/R models.


CONCLUSIONS
Although insulin has been reported to provide anti-inflammatory benefits by reducing oxidative and nitrosative stress and cytokine release, none of these protective effects was seen in the three I/R-induced liver injury models we tested.
Chen
C F
CF
Division of Gastroenterology, Department of Internal Medicine, Cheng Hsin General Hospital, and School of Health, Ming Chuan University, Taipei, Taiwan.
Leu
F J
FJ
Chen
H I
HI
Wang
D
D
Chou
S J
SJ
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D004195:Disease Models, Animal; D006499:Hepatic Artery; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D007328:Insulin; D001219:Aspartate Aminotransferases