Significance of insulin signaling in liver regeneration triggered by portal vein ligation

Background: To investigate the role of insulin signaling in liver regeneration following portal vein ligation (PVL). Materials and Methods: Streptozotocin-induced insulin-deficient rats underwent PVL, and were sacrificed at indicated time points. Liver regeneration indices, including volumetric shifting, BrdU, proliferative cell nuclear antigen (PCNA), and Ki-67 labeling index, were determined. Cell cycle markers, telomerase reverse transcriptase (TERT), and apoptosis-related genes were detected using quantitative real time polymerase chain reaction (PCR). Cell cycle analysis was determined using flow cytometry. Expression of insulin-like growth factor receptor (IGFR)-2 and TGFβ1 were determined using Western blot. Results: Restituted liver mass and redistributed volume ratio of insulin-deficient rats were decreased compared with those of normal rats. Labeling index of BrdU and PCNA of insulin-deficient rats were increased compared with normal rats, evidenced by an increased S-phase fraction detected by flow cytometry. Expression of cyclin A2, cyclin B1, TERT mRNA, and telomerase activity were decreased in insulin-deficient rats. Increased Bax, Daxx, and JNK mRNA expression and decreased Bcl X_L expression in insulin-deficient rats, led to increased hepatocyte apoptosis than normal rats. Finally, expression of IGFR-2 was increased in insulin-deficient rats. Conclusions: Insulin signaling plays an important role in liver regeneration triggered by portal vein ligation.