The role of insulin, insulin-like growth factor-I and growth hormone in counteracting dexamethasone induced nitrogen wasting in rats.
Administration of glucocorticoids is associated with decreased nitrogen balance. The main aim of the present study was to elucidate whether this could be counteracted by subcutaneous infusions of rhGH (360 micrograms/d), rhIGF-1 (500 micrograms/d) or insulin (39 micrograms/d). During a study period of 8 days one out of 10 groups of rats received dexamethasone (dex, 26 micrograms/d) alone, whereas 7 groups were given one or more of the three peptides in combination with dex. One group was given saline alone and one was food restricted to match the average food intake among dex groups. Food restriction and saline alone produced relative nitrogen balances, retained N/ingested N (x100) of 44 (SE 3) and 36% (SE 4), respectively. This was decreased (p < 0.001) to 7% (SE 3) with dex alone. However, if either insulin/rhGH/rhIGF-1, rhIGF-1 alone or insulin/rhIGF-1 were given together with dex, the relative nitrogen balances increased significantly (p < 0.03) up to 16, 22 and 24% (SE 3), respectively. Insulin or rhGH alone were without effect as was rhGH combined with either rhIGF-I or insulin. Although the relative nitrogen balances associated with insulin/rhIGF-1 and rhIGF-1 alone were not found to be significantly different, the former infusion regimen produced a significantly (p < 0.02) lower plasma urea. It is concluded that in the rat, rhIGF-1 has a potential to counteract the decrease in nitrogen balance induced by potent glucocorticoids, whereas rhGH as administered in this experiment does not have this effect.
Malmlöf
K
K
Department of Pharmacology, Biopharmaceuticals R & D, Pharmacia & Upjohn, Stockholm, Sweden.
Arrhenius-Nyberg
V
V
Saxerholt
H
H
Skottner
A
A
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004435:Eating; D005508:Food Deprivation; D019382:Human Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D007328:Insulin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D009584:Nitrogen