Hepatic regeneration in insulin-like growth factor binding protein-1 transgenic mice.
OBJECTIVE
Partial hepatectomy results in activation of genes in the residual liver tissue which serve to restore glucose homeostasis and regenerate liver mass. Expression of insulin-like growth factor binding protein-1 (IGFBP-1) is up-regulated following partial hepatectomy and IGFBP-1 can modulate both the metabolic and mitogenic effects of insulin-like growth factor-1 (IGF-I). The aim of the study was to compare the effects of partial hepatectomy on blood glucose levels and hepatic regeneration in wild-type and transgenic mice which constitutively overexpress IGFBP-1.


METHODS
Hepatic IGFBP-1 mRNA, blood glucose concentrations, liver mass and hepatic DNA synthesis were compared in sham-operated and partially hepatectomized transgenic and wild-type mice.


RESULTS
Hepatic IGFBP-1 mRNA was higher in sham-operated transgenic than wild-type mice, but in both groups of mice, partial hepatectomy was associated with a significant rise in IGFBP-1 mRNA. The absolute decline in blood glucose levels following partial hepatectomy was greater in transgenic mice. Basal DNA synthesis and the response to IGF-I in isolated hepatocytes from both groups of mice were similar, and DNA synthesis in the regenerating liver in vivo was not significantly different in transgenic as compared to wild-type mice: 449.3 +/- 63.9 vs. 321.6 +/- 52.3 cpm/microgram DNA. Hepatic regeneration as measured by liver weight after hepatectomy was not different between transgenic and wild-type mice.


CONCLUSIONS
Constitutive overexpression of IGFBP-1 does not enhance hepatic regeneration and does not prevent the decline in blood glucose following partial hepatectomy.
Liu
Y Y
YY
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Rajkumar
K
K
Murphy
L J
LJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006498:Hepatectomy; D007328:Insulin / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008115:Liver Regeneration; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004247:DNA