IGF-II receptors and IGF-II-stimulated glucose transport in human fat cells.
Insulin-like growth factor II (IGF-II) receptors have been described in rat but not in human adipocytes. In both species, IGF-II has been reported to stimulate glucose transport by interacting with the insulin receptor. In this study, we have unequivocally demonstrated the presence of IGF-II receptors in human adipocytes. 125I-labeled IGF-II specifically binds to intact adipocytes, membranes, and lectin-purified detergent solubilized extracts. Through the use of 0.5 mM disuccinimidyl suberate, 125I-IGF-II is cross-linked to a 260-kDa protein that is identified as the IGF-II receptor by displacement experiments with unlabeled IGF-II, IGF-I, and insulin and either by immunoprecipitation or by Western blot analysis with mannose 6-phosphate receptor antibodies. The concentrations of IGF-II required for half-maximal and maximal stimulation of glucose transport in human adipocytes are 35 and 100 times more than that of insulin. The possibility of IGF-II stimulating glucose transport by interacting predominantly with the insulin receptor is suggested by the following: 1) the concentration of IGF-II that inhibits half of insulin binding is only 20 times more than that of insulin; 2) the lack of an additive effect of IGF-II and insulin for maximal stimulation of glucose transport; 3) the ability of monoclonal insulin receptor antibodies to decrease glucose transport stimulated by submaximal concentrations of both IGF-II and insulin; and 4) the ability of IGF-II to stimulate insulin receptor autophosphorylation albeit at a reduced potency when compared with insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
Sinha
M K
MK
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
Buchanan
C
C
Raineri-Maldonado
C
C
Khazanie
P
P
Atkinson
S
S
DiMarchi
R
R
Caro
J F
JF
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin; D005947:Glucose