The interaction of proinsulin with the insulin-like growth factor-I receptor in human liver, muscle, and adipose tissue.
Because of the sequence homology and tertiary structure similarities between proinsulin (PI) and insulin-like growth factor-I (IGF-I), it is possible that PI interacts with the IGF-I receptor with higher affinity than insulin. To test this hypothesis in man, we have partially purified IGF-I receptors from liver, muscle, and adipose tissue and studied their interaction with PI, insulin, IGF-I, and IGF-II. With some tissue to tissue variation, [125I]insulin binding was 4- to 8-fold greater than IGF-I binding. Unlabeled IGF-I at about 1 x 10(-9 M, IGF-II at about 1 x 10(-8) M, and insulin at about 1 x 10(-6) M displace 50% the binding of [125I]IGF-I to its receptor, whereas PI at 1 x 10(-6) M displaces less than 20% of the binding of [125I]IGF-I to its receptor. We conclude that in human liver, muscle, and adipose tissue, PI does not interact with the IGF-I receptor at a higher affinity than insulin, and the affinity of IGF-I receptors is several-fold lower than that of insulin receptors. It is, therefore, unlikely that if PI were to be administered to man any of its biological effects would be by interacting with the IGF-I receptor.
Burguera
B
B
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
Frank
B H
BH
DiMarchi
R
R
Long
S
S
Caro
J F
JF
D000273:Adipose Tissue / Q000378:metabolism*; D001667:Binding, Competitive; D002102:Cadaver; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D011384:Proinsulin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000378:metabolism
D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011384:Proinsulin