Plasma clearance and tissue distribution of labelled insulin-like growth factor-I (IGF-I), IGF-II and des(1-3)IGF-I in rats.
Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 degrees C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1-3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1-3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1-3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4.59, 1.20 and 1.34 ml/min per kg respectively. The mean steady-state volume of distribution was larger for des(1-3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1-3)IGF-I greater than IGF-I greater than IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo.
Ballard
F J
FJ
CSIRO Division of Human Nutrition, Adelaide, South Australia.
Knowles
S E
SE
Walton
P E
PE
Edson
K
K
Owens
P C
PC
Mohler
M A
MA
Ferraiolo
B L
BL
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000493:pharmacokinetics; D007335:Insulin-Like Growth Factor II / Q000493:pharmacokinetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010446:Peptide Fragments / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000378:metabolism; D013002:Somatomedins / Q000493:pharmacokinetics*
D010446:Peptide Fragments; D013002:Somatomedins; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II