EXPRESSION OF IGFBP-1 IN NORMAL AND CIRRHOTIC HUMAN LIVERS

Cirrhosis of the liver, a condition characterised by hepatocyte regene ration, is also associated with elevated insulin levels and insulin re sistance. In animal models hepatic regeneration is associated with inc reased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonst rate a negative correlation with IGFBP-1 levels. To further our unders tanding of the regulation of IGFBP-1 in cirrhosis we have studied stea dy state levels of IGFBP-1 mRNA in human liver horn three groups of pa tients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic Liver transplantation (n=4); group 2, patients undergo ing major liver resection with no histological evidence of chronic liv er disease (n=4); and group 3, patients undergoing orthotopic transpla ntation for chronic liver failure (n=9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patie nts IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin. IGFBP-1 mRNA was detectable in all the human liver sample s with the greatest levels seen from the normal livers of group 2 pati ents. Insulin levels were elevated in the cirrhotic group 3 patients c ompared to a normal range as were IGFBP-1 levels. There was no relatio nship between circulating levels of IGFBP-1 and IGFBP-1 gene expressio n. In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of ins ulin suggesting that there are factors other than insulin regulating I GFBP-1 gene expression.