Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia.
Insulin-like growth factors (IGFs) in blood form two complexes with specific binding proteins (BPs): a large, growth hormone (GH)-dependent complex with restricted capillary permeability, and a smaller complex, inversely related to GH, with high turnover of its IGF pool and free capillary permeability. The distribution of BPs and of IGFs I and II between these complexes was studied in sera from healthy adults treated with IGF I or/and GH and from patients with extrapancreatic tumor hypoglycemia. Like GH, IGF I administration raises IGF I and two glycosylation variants of IGFBP-3 in the large complex, but unlike GH drastically reduces IGF II. During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively. GH treatment, associated with elevated insulin levels, suppresses IGFBP-2 and inhibits its increase owing to infused IGF I. The small complex of tumor sera contains increased amounts of IGFBP-2 and -3, and two- to threefold elevated IGF II.


CONCLUSIONS
low GH and/or insulin during IGF I infusion and in extrapancreatic tumor hypoglycemia enhance expression of IGFBP-2 and favor partition of IGFBP-3 into the small complex. Free capillary passage and high turnover of its increased IGF I or II pools may contribute to compensate for suppressed insulin secretion during IGF I infusion or to development of tumor hypoglycemia.
Department of Medicine, University Hospital of Zürich, Switzerland.
J
J
Zapf
C
C
Schmid
H P
HP
Guler
M
M
Waldvogel
C
C
Hauri
E
E
Futo
P
P
Hossenlopp
M
M
Binoux
E R
ER
Froesch
D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D046911:Macromolecular Substances; D008970:Molecular Weight; D009369:Neoplasms / Q000150:complications*; D013002:Somatomedins / Q000378:metabolism* / Q000494:pharmacology*
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D046911:Macromolecular Substances; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone