INSULIN PRETREATMENT PROTECTS THE LIVER FROM ISCHEMIC DAMAGE DURING PRINGLES MANEUVER

Background. Although maintenance of adenosine triphosphate (ATP) level s is important to restore liver functions during anoxia, ATP productio n by oxidative phosphorylation is inhibited during Pringle's maneuver, and only a little ATP can be supplied by glycolysis. The glycolytic a ctivity of the liver is controlled by the nutritional condition and ho rmones. Enhancement of glycolytic activity by insulin may increase ATP production and thus may protect the liver from ischemia. Methods. Rat s 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 per iod) before portal triad clamping (PTC) was performed. After laparotom y was performed, PTC was performed for 30 minutes. The fructose 2,6-bi sphosphate (F-2,6-BP) level, the hepatic levels of lactate and ATP, th e bile flow rate, the plasma levels of aspartate transaminase and lact ate dehydrogenase, and the indocyanine green clearance were measured a t appropriate times. Results. The hepatic F-2,6-BP levels before PTC i n 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 glycol ytic activity of the insulin group before PTC was significantly enhanc ed compared with that of the other groups. Lactate was more rapidly ac cumulated in livers of the insulin group during PTC than in those of t he other groups. The ATP levels and energy charge during PTC of the in sulin group were higher than those of the other groups. The bile flow rate and indocyanine green clearance after PTC were restored in the or der of the insulin, fed, and fasted groups. Conclusions. Insulin admin istration before PTC increased the hepatic F-2,6-BP content and enhanc ed glycolytic activity. Insulin pretreatment combined with feeding imp roved the hepatic energy metabolism during PTC and restored the liver functions after PTC. Insulin has protective effects on the liver durin g PTC.