Acid-labile subunit regulation during the early stages of liver regeneration: implications for glucoregulation.
The initiation of liver regeneration is regulated by endogenously produced growth factors and cytokines and is accompanied by suppression of growth hormone (GH) binding to hepatocytes. We have demonstrated some of these factors, particularly GH, which modulate acid-labile subunit (ALS) expression in vitro. Consequently, we investigated ALS hepatic mRNA and serum levels in rats for 24 h after partial hepatectomy (PHx). There was a significant suppression of ALS gene expression (approximately 50%, P < 0.005) and serum levels (approximately 30%, P < 0.02) by 12 h in PHx rats relative to controls. Relative to intact animals, hepatic mRNA and serum levels of ALS were suppressed by approximately 60% at 24 h. Similarly, hepatic GH receptor mRNA levels were significantly reduced in PHx animals. Moreover, hepatocytes isolated from PHx animals were less responsive to GH than those from controls. Overall, our results demonstrate that suppression of ALS gene expression and serum levels during liver regeneration relates to lowered hepatic GH sensitivity. Suppressed circulating ALS may alter insulin-like growth factor bioavailability and constitute a mechanism to maintain relatively normal glucoregulation after loss of liver mass.
Delhanty
P J
PJ
Department of Molecular Medicine, University of Sydney, Kolling Institute of Medical Research, St. Leonards, New South Wales 2065, Australia. delhanty@med.usyd.edu.au
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D000818:Animals; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D013006:Growth Hormone / Q000502:physiology; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008115:Liver Regeneration / Q000502:physiology*; D008894:Milk Proteins; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000235:genetics; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D015415:Biomarkers; D001786:Blood Glucose; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D008894:Milk Proteins; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose