Insulin pretreatment protects the liver from ischemic damage during Pringle's maneuver.
BACKGROUND
Although maintenance of adenosine triphosphate (ATP) levels is important to restore liver functions during anoxia, ATP production by oxidative phosphorylation is inhibited during Pringle's maneuver, and only a little ATP can be supplied by glycolysis. The glycolytic activity of the liver is controlled by the nutritional condition and hormones. Enhancement of glycolytic activity by insulin may increase ATP production and thus may protect the liver from ischemia.


METHODS
Rats were divided into three groups: fasted group, food was withheld for 24 hours; fed group, food was provided ad libitum; and insulin group, fed rats were administered insulin (12 units/kg during a 30-minute period) before portal triad clamping (PTC) was performed. After laparotomy was performed, PTC was performed for 30 minutes. The fructose 2,6-bisphosphate (F-2,6-BP) level, the hepatic levels of lactate and ATP, the bile flow rate, the plasma levels of aspartate transaminase and lactate dehydrogenase, and the indocyanine green clearance were measured at appropriate times.


RESULTS
The hepatic F-2,6-BP levels before PTC in the fasted, fed, and insulin groups were 6.2 +/- 3.8, 55.6 +/- 10.6, and 122.2 +/- 31.3 nmol/gm dry weight liver, respectively. The glycolytic activity of the insulin group before PTC was significantly enhanced compared with that of the other groups. Lactate was more rapidly accumulated in livers of the insulin group during PTC than in those of the other groups. The ATP level and energy charge during PTC of the insulin group were higher than those of the other groups. The bile flow rate and indocyanine green clearance after PTC were restored in the order of the insulin, fed, and fasted groups.


CONCLUSIONS
Insulin administration before PTC increased the hepatic F-2,6-BP content and enhanced glycolytic activity. Insulin pretreatment combined with feeding improved the hepatic energy metabolism during PTC and restored the liver functions after PTC. Insulin has protective effects on the liver during PTC.
First Department of Surgery, Osaka University Medical School, Suita, Japan.
Y
Y
Morimoto
T
T
Nishida
W
W
Kamiike
H
H
Mizuno
H
H
Kazuo
E
E
Furuya
H
H
Matsuda
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003250:Constriction; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries*; D008297:Male; D010085:Oxidative Phosphorylation; D011169:Portal Vein; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*
D000227:Adenine Nucleotides; D007328:Insulin; D000255:Adenosine Triphosphate