Enhanced expression of insulin-like growth factor-binding protein-I in the fasted rat: the effects of insulin and growth hormone administration.
The effect of fasting on insulin-like growth factor-binding protein-1 (IGFBP-1) expression was examined in the rat. Food deprivation for a period of 24 h resulted in a 9.5 +/- 2.0-fold increase in hepatic IGFBP-1 mRNA abundance (P less than 0.001). An increase in circulating IGFBP-1 in sera from fasted rats was demonstrated by immunoblotting, and an increased abundance of a 30-kDa IGFBP in sera from fasted rats was apparent when [125I]IGF-I was used in ligand blotting experiments. Refeeding resulted in a prompt decline in hepatic IGFBP-1 mRNA. Administration of insulin (0.5-4 U, ip) to fasted rats resulted in profound hypoglycemia, but either increased or had no significant effect on hepatic IGFBP-1 mRNA abundance. In contrast, administration of human GH (hGH; 100 micrograms, ip) resulted in a prompt decline in hepatic IGFBP-1 mRNA, followed by a late rebound in IGFBP-1 mRNA to levels greater than those in fasted controls. Furthermore, hepatic IGFBP-1 mRNA levels were significantly lower in hGH-treated (100 micrograms every 8 h) food-deprived rats than in saline-treated food-deprived rats (2.25 +/- 1.55- vs. 8.99 +/- 3.80-fold increase; P less than 0.005). Similar changes were observed when serum IGFBP-1 was quantitated by immunoblotting. The effects of GH could not be explained by secondary hyperinsulinism, since no significant increase in insulin levels was observed in GH-treated rats. From these observations we conclude the enhanced expression of IGFBP-1 in the food-deprived rat may be a consequence of GH deficiency rather than insulin deficiency.
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
L J
LJ
Murphy
C
C
Seneviratne
P
P
Moreira
R E
RE
Reid
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005215:Fasting; D013006:Growth Hormone / Q000097:blood / Q000494:pharmacology*; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013006:Growth Hormone