Insulin-like growth factor binding protein-1 induces insulin release in the rat.
Injections of human insulin-like growth factor binding protein (hIGFBP-1) are reported to induce hyperglycemia in the rat, suggesting that IGFBP-1 acutely regulates glucose homeostasis. We now report the effects on glucose and insulin levels of administering recombinant (r) hIGFBP-1. In a series of studies, normal and streptozotocin (STZ) diabetic male Wistar rats (180-210 g), fasted for 6 or 16 h, were injected with rhIGFBP-1 (i.v., 80-500 microg/rat). rhIGFBP-1 did not affect blood glucose acutely but did stimulate insulin release in normal rats (5 min post injection; PBS, 103.5 +/- 8.5; rhIGFBP-1 (500 microg), 166.8 +/- 15.7; rhIGFBP-1 (100 microg); 151.4 +/- 14.1% initial). rhIGFBP-1 pretreatment, in normal and diabetic rats, reduced the hypoglycemic response to rhIGF-I (diabetic rats after 20 min: PBS, 103.4 +/- 11.4; BP-1 (500 microg) +/- rhIGF-I (50 microg), 97.6 +/- 3.6; rhIGF-I, 48.2 +/- 4.3% initial) but did not affect the hypoglycemic response to des(1-3)IGF-I or insulin (0.5 U/kg). These studies show that rhIGFBP-1 causes insulin release, has a minimal effect on blood glucose, and inhibits the hypoglycemic effect of rhIGF-I. These data suggest that endogenous IGF-I tonically suppresses insulin secretion and imply that aberrant IGFBP levels or reduced IGF-I bioactivity may lead to chronic hyperinsulinemia.
Mortensen
D L
DL
Department of Endocrinology, Genentech, Inc., South San Francisco, California 94080, USA.
Won
W B
WB
Siu
J
J
Reifsnyder
D
D
Gironella
M
M
Etcheverry
T
T
Clark
R G
RG
D000818:Animals; D001667:Binding, Competitive; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D005215:Fasting; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I