Response of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) and IGFBP-3 to IGF-I treatment in severe insulin resistance.
It has been suggested that recombinant human IGF-I (rhIGF-I) is a potential therapeutic agent in diabetes mellitus. It is known to have glucose-lowering effects in normal individuals, in patients with non-insulin-dependent diabetes (NIDDM) and in extreme insulin-resistant states. IGF-binding proteins (IGFBPs) have the potential to affect the biological activity of rhIGF-I. We have studied the effect of infused rhIGF-I on IGFBP-1 and IGFBP-3 in a patient with Mendenhall's syndrome, a rare insulin-resistant state. During an infusion of 20 mg rhIGF-I, glucose concentrations fell from 44.1 +/- 7.2 to 31.5 +/- 7.2 (S.E.M.) mmol/l (P = 0.001), and insulin and C-peptide levels fell from 920 +/- 62 to 542 +/- 45 mU/l (P = 0.008) and 5466 +/- 633 to 3071 +/- 297 pmol/l (P = 0.02) respectively. Significant lowering of phosphate, magnesium and alkaline phosphatase concentrations was also noted. IGF-I levels rose from 48 +/- 10.2 to 410 +/- 50.1 micrograms/l (P = 0.001), and those of IGF-II fell from 279.8 +/- 8.3 to 104.3 +/- 7.9 micrograms/l (P = 0.001). IGFBP-1 concentrations did not significantly change during the infusion but those of IGFBP-3 increased from 1655 +/- 127 to 2197 +/- 334 micrograms/l (P = 0.002), despite a significant fall in GH concentrations from 10.7 +/- 2.6 to 4.1 +/- 1.1 mU/l (P = 0.007), suggesting that IGFBP-3 regulation is also IGF-I-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Quin
J D
JD
Department of Medicine, King's College School of Medicine, London, UK.
Checkley
A
A
Gallagher
A
A
Jones
J
J
MacCuish
A C
AC
Miell
J P
JP
D000052:Acanthosis Nigricans / Q000378:metabolism; D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002352:Carrier Proteins / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D006130:Growth Disorders / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D013577:Syndrome
D001786:Blood Glucose; D002096:C-Peptide; D002352:Carrier Proteins; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II