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).


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.
Tseng
Jeng-Hwei
JH
Department of Radiology, Chang Gung Memorial Hospital, Chang Gung University, Taipei.
Ouyang
Chun-Hsiang
CH
Lin
Kun-Ju
KJ
Yeh
Ta-Sen
TS
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008026:Ligation; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011169:Portal Vein; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D007328:Insulin; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D017527:Receptor, IGF Type 2; D053773:Transforming Growth Factor beta1; D001973:Bromodeoxyuridine