The ability of
insulin-like growth factor-I (
IGF-I) to protect against losses of body
protein during periods of dietary
nitrogen restriction has been evaluated in young rats. Recombinant human
IGF-I was administered by osmotic pumps at dose rates of 0, 1.2 or 2.9 mg/kg per day over a 7-day period beginning with the transfer of animals from an 18% to a 4%
protein diet. A fourth group received the potent truncated
IGF-I analogue,
des(1-3)IGF-I, at a dose of 1.2 mg/kg per day over a comparable 7-day period. Plasma
IGF-I levels were reduced by 60% following
nitrogen restriction, a reduction that was partly prevented by
IGF-I administration, especially at the higher dose, but not measurably by
des(1-3)IGF-I. The major
IGF-binding protein circulating in blood,
IGFBP-3, demonstrated a similar pattern of change. A significant (P less than 0.05) protection of
body weight was achieved in the low dose
IGF-I and
des(1-3)IGF-I groups, but only after differences in food intake had been eliminated by analysis of covariance.
Nitrogen balances were not significantly different unless analysis of covariance was used to adjust for the
nitrogen intakes, whereupon all treatment groups showed improved balance, especially the animals treated with the low
IGF-I dose and
des(1-3)IGF-I (both P less than 0.01). The rate of
muscle protein breakdown calculated from the urinary excretion of 3-methyl-histidine was not significantly altered by the treatments, but fell progressively throughout the 7 days. The fractional rate of
muscle protein synthesis measured on the final day was increased by 31,26 and 21% respectively by the low and high doses of
IGF-I and by
des(1-3)IGF-I. Organ weights (g/kg
body weight) showed no effects of
IGF-I treatment except for 16% increases in the weight of kidneys in the high dose
IGF-I and the
des(1-3)IGF-I groups. Carcass analyses demonstrated higher water and lower fat contents (all P less than 0.01) in the same groups. These results suggest that exogenous
IGF-I and especially
des(1-3)IGF-I can partly protect body
protein reserves during
nitrogen restriction.