Insulin in University of Wisconsin solution exacerbates the ischemic injury and decreases the graft survival rate in rat liver transplantation.
BACKGROUND
Insulin keeps the liver in a metabolically vigorous state. However, organ preservation aims to decrease the metabolic rate. The objective of this study was to clarify the effect of insulin used in University of Wisconsin (UW) preservation solution on the liver graft.


METHODS
The liver grafts were preserved by UW solution with or without insulin for 7, 9, and 24 hr, respectively. The influence of insulin was studied by 7-day survival rate, liver function, morphology, and intragraft gene expression 24 hr after transplantation. Morphology was studied on the preserved grafts.


RESULTS
The morphology of the graft in the insulin group showed more severe ischemia-reperfusion injury. The 7-day graft survival rates of the 7-hr subgroups with and without insulin were 55% and 93%, respectively (P=0.02). In the 9-hr subgroups, the survival rates were 0% and 78%, respectively (P=0.002). The serum levels of aspartate aminotransferase (AST) (P=0.008) and alanine aminotransferase (ALT) (P=0.032) were higher in the 7-hr subgroup with insulin. The same trend was found in the 9-hr subgroups (AST, P=0.016; ALT, P=0.016). The expression level of 215 genes were much lower at 24 hr after transplantation in the grafts preserved with insulin than in those preserved without insulin, and most of the genes were related to metabolic activities.


CONCLUSIONS
Insulin in UW solution may exacerbate graft ischemic injury and decrease the graft survival rate in rat liver transplantation. Insulin, in the absence of glucose in UW solution, may exhaust the metabolic activity of the liver graft. It is harmful rather than helpful for isolated rat liver grafts preserved in UW solution.
Li
Xian-Liang
XL
Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong, China.
Man
Kwan
K
Liu
Yong-Feng
YF
Lee
Terence Kin-Wah
TK
Tsui
Steven Hong-Teng
SH
Lau
Chi-Keung
CK
Lo
Chung-Mau
CM
Fan
Sheung-Tat
ST
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D017209:Apoptosis; D005786:Gene Expression Regulation; D005978:Glutathione; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000473:pathology* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000503:physiopathology*; D013997:Time Factors; D014185:Transplantation, Isogeneic
D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose