The expression pattern of energy metabolic genes regulated by insulin through the IRS-2 pathway in the liver graft preserved by UW solution

Abstract

Background:The expression of the genes related to glucose, fatty acid and lipoprotein metabolism are tightly regulated by insulin.The energy status is directly related to the ischemia-reperfusion injury and the outcome of transplantation. However, the expression of energy genes during preservation remains unknown. Objective: To investigate the expression pattern of energy genes regulated by insulin in the liver graft preserved by UW solution. Methods: Liver grafts were harvested from Lewis rats and preserved by UW solution with (UWI) or without (UW) insulin.Samples were collected at 0, 3, 7, 9 and 24 hours, respectively. The expression of glucokinase (GCK), fatty acid synthase (FAS), apolipoprotein C-III (ApoC-III), sterol regulatory element binding protein-1c (SREBP-1c), insulin growth like factor binding protein-1 (IGFBP-1) and insulin receptor substrate-2 (IRS-2) genes were compared by RT-PCR. The intragraft levels of ATP, total adenine nucleotides (TAN), energy charge (EC) were detected by HPLC. Results: The expression of GCK was upregulated in UWI group than that of UW group. The expression levels decreased at 7 and 24 hours. The similar trends could be found on the expression of SREBP-1 and IRS-2. The ApoC-III expression was also upregulated in UWI group. Fas was upregulated in UW group and the expression levels decreased gradually. On the contrary, the highest expression level of Fas was found at 24 hours in UWI group. The expression of IGFBP-1 was very weak both in UWI and UW groups. The ATP levels showed significant differences between the groups at 7 (P=0.017), 9 (P=0.001) and 24 hours (P=0.011). Insulin decreased the ATP level during the preservation. The similar trends were found in TAN and EC levels. However, the EC level was significant higher in UWI group than that of UW group at 0 hour (0.436/0.342, P=0.032). Conclusion: Insulin in UW solution can exacerbate the ATP depletion and decrease the TAN and EC levels which directly accelerate the ischemia-reperfusion injury. The glycogen utilization and the metabolism of fatty acid and lipoprotein were regulated by insulin through the SREBP-1c and IRS-2 pathway during the cold preservation by UW solution.