Recombinant human insulin-like growth factor I induces its own specific carrier protein in hypophysectomized and diabetic rats.
The physiology of the specific serum binding proteins which constitute the main storage pool for insulin-like growth factors (IGFs) in mammals is still incompletely understood. We have, therefore, investigated the regulation of these proteins in (i) hypophysectomized (hypox) rats infused with recombinant human growth hormone (rhGH) or recombinant human IGF 1 (rhIGF I) and (ii) streptozotocin-diabetic rats infused with insulin or rhIGF I. The main carrier protein, a GH-dependent complex of apparent molecular mass 200 kDa, contains N-glycosylated IGF-binding subunits (42, 45, and 49 kDa) that differ in their glycosyl but not in their protein moiety. These subunits are lacking in hypox and diabetic rats. They are induced by GH and insulin, respectively, and appear in the 200-kDa complex. Infusion of rhIGF I induces the subunits in both states; however, only in diabetic, not in hypox, rats do they form the 200-kDa complex. Glycosylated carrier protein subunits do not appear before 8 hr of rhIGF I infusion. During that period, hypox rats may become severely hypoglycemic. After 16 hr, glycosylated subunits are clearly induced, and blood sugar values are normal. We conclude: (i) The N-glycosylated subunits of the 200-kDa complex reflect the IGF I status. (ii) IGF I may mediate the induction of these subunits by GH. (iii) Significant association to the 200-kDa complex occurs only in the presence of GH. It is likely that GH, but not IGF I, induces a component, which itself does not bind IGF, but associates with the glycosylated IGF-binding subunits. (iv) The glycosylated subunits protect against IGF-induced hypoglycemia and may be involved in tissue-specific targeting of IGFs.
Zapf
J
J
Department of Medicine, University Hospital, Zurich, Switzerland.
Hauri
C
C
Waldvogel
M
M
Futo
E
E
Häsler
H
H
Binz
K
K
Guler
H P
HP
Schmid
C
C
Froesch
E R
ER
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006023:Glycoproteins / Q000096:biosynthesis*; D013006:Growth Hormone / Q000494:pharmacology / Q000502:physiology; D007016:Hypophysectomy; D007328:Insulin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D051381:Rats; D011994:Recombinant Proteins; D013002:Somatomedins / Q000494:pharmacology*
D002352:Carrier Proteins; D006023:Glycoproteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone