GLP-1 infusion reduces IGFBP-1 serum level in humans.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) and the insulin-like growth factor (IGF) system are important factors in metabolic regulation and cellular growth. Interactions between the systems exist but these are vaguely explored and only in vitro, where GLP-1 has been reported to stimulate IGF-binding protein 1 (IGFBP-1). This study, therefore, aimed to elucidate the effects of GLP-1 on IGF-I and the IGFBPs, which regulate IGF-I bioactivity.


METHODS
We investigated the effects of a 2-hour intravenous GLP-1 infusion on the IGF system in 12 overnight fasted healthy humans, using a randomized, double-blinded, cross-over study design. Serum samples were assessed for immunoreactive levels of IGF-I, IGFBP-1 and -2 as well as for bioactive IGF-I, which was determined by a cell-based IGF-I kinase receptor activation assay.


RESULTS
GLP-1 infusion markedly increased insulin levels (p<0.0001), reduced IGFBP-1 levels (p=0.02), and tended to increase IGF-I bioactivity (p=0.06). There were no significant changes in IGFBP-2 or immunoreactive IGF-I levels.


CONCLUSIONS
In this short-term study, GLP-1 reduced IGFBP-1 levels in vivo and tended to increase IGF-I bioactivity. The IGFBP-1 outcome is opposite to the in vitro situation, hereby demonstrating that in vivo the ability of GLP-1 to stimulate insulin and hereby suppress IGFBP-1 outweighs any direct stimulatory effects of GLP-1 on IGFBP-1.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark; Novo Nordisk A/S, Bagsvaerd, Denmark. Electronic address: jsk@dadlnet.dk.
Jeppe
J
Skov
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark; Medical Research Laboratory, Institute of Clinical Medicine, Faculty of Health, Aarhus University, Denmark.
Jan
J
Frystyk
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark.
Jens Sandahl
JS
Christiansen
D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000187:drug effects; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010919:Placebos; D055815:Young Adult
C032231:IGFBP1 protein, human; C577903:IGFBP2 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D010919:Placebos; D007334:Insulin-Like Growth Factor I; D052216:Glucagon-Like Peptide 1
Bioactive IGF-I; GLP-1; IGF-I; IGFBP; Insulin