Abstract

ObjectiveGlucagon-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. DesignWe 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. ResultsGLP-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. ConclusionIn 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.

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