GLP-1 infusion reduces IGFBP-1 serum level in humans

Growth Horm IGF Res. 2014 Apr-Jun;24(2-3):67-70. doi: 10.1016/j.ghir.2014.01.003. Epub 2014 Jan 18.

Abstract

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.

Design: 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.

Conclusion: 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.

Keywords: Bioactive IGF-I; GLP-1; IGF-I; IGFBP; Insulin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Double-Blind Method
  • Down-Regulation / drug effects
  • Glucagon-Like Peptide 1 / administration & dosage*
  • Humans
  • Infusions, Intravenous
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / drug effects
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Insulin-Like Growth Factor Binding Protein 2 / drug effects
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Placebos
  • Young Adult

Substances

  • IGFBP1 protein, human
  • IGFBP2 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 2
  • Placebos
  • Insulin-Like Growth Factor I
  • Glucagon-Like Peptide 1