Further characterisation of an IGF-I enhancing antibody: actions on IGF-I-induced hypoglycaemia and interaction with the analogue LR3IGF-I.
We have previously shown that a polyclonal anti-IGF-I antiserum administered together with IGF-I potentiates IGF-I activity in vivo. The anti-IGF-I antiserum has a modest affinity for IGF-I, similar to that for enhancing IGFBPs, and treated animals have significantly higher circulating IGF-I concentrations than their controls. Our recent findings have demonstrated that the anti-IGF-I activity decreases the clearance of IGF-I by at least 2-fold and that it abolishes the acute hypoglycaemic action of a single subcutaneous dose of IGF-I. Interestingly, we have been unable to demonstrate potentiation of the growth-promoting activity of the potent non-IGFBP binding IGF-I analogue LR3IGF-I, even though the analogue binds to the antiserum in vitro; rather native IGF-I/antibody complexes perform even better than LR3IGF-I. In IGF-I/antibody-treated dwarf rats, most IGF-I may be found in an uncharacterised high molecular weight antibody complex which is probably responsible for improved IGF-I performance. Thus, the anti-IGF-I antibody may be behaving in a similar manner to a high molecular weight IGFBP and is effective in potentiating IGF-I action in vivo.
Pell
J M
JM
Babraham Institute, Cambridge, U.K.
Flick-Smith
H C
HC
Dye
S
S
Hill
R A
RA
D000818:Animals; D019138:Antibodies, Blocking / Q000502:physiology*; D000917:Antibody Formation; D001835:Body Weight; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008657:Metabolic Clearance Rate; D051381:Rats; D014018:Tissue Distribution
D019138:Antibodies, Blocking; C084339:LR(3)IGF-I; D007334:Insulin-Like Growth Factor I