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

J Surg Res. 2011 Mar;166(1):77-86. doi: 10.1016/j.jss.2009.06.043. Epub 2009 Jul 30.


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.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Cycle / physiology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Disease Models, Animal
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Insulin / metabolism*
  • Ki-67 Antigen / metabolism
  • Ligation
  • Liver Diseases / diagnosis
  • Liver Diseases / metabolism*
  • Liver Diseases / physiopathology
  • Liver Regeneration / physiology*
  • Male
  • Portal Vein
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, IGF Type 2 / metabolism
  • Signal Transduction / physiology*
  • Tomography, Emission-Computed, Single-Photon
  • Tomography, X-Ray Computed
  • Transforming Growth Factor beta1 / metabolism


  • Insulin
  • Ki-67 Antigen
  • Proliferating Cell Nuclear Antigen
  • Receptor, IGF Type 2
  • Transforming Growth Factor beta1
  • Bromodeoxyuridine