Arginine induces IGF-1 secretion from the endoplasmic reticulum

Biochem Biophys Res Commun. 2019 Jul 5;514(4):1128-1132. doi: 10.1016/j.bbrc.2019.05.044. Epub 2019 May 14.

Abstract

Arginine is a semi-essential amino acid with multiple functions, including stimulating the secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). IGF-1, which is produced by hepatocytes, plays important roles in cellular metabolism, proliferation, and growth. Previous studies showed that arginine-induced IGF-1 secretion occurs via two pathways: a GH-dependent pathway and an arginine-dependent pathway with an unknown mechanism. In this study, we identified the mechanisms regulating IGF-1 secretion. First, GH stimulates the translation of IGF-1 and increases IGF-1 protein levels, leading to IGF-1 secretion. As observed in fasted mice and hepatocytes cultivated in arginine-depleted medium, decreases in arginine concentrations resulted in IGF-1 retention in the endoplasmic reticulum. Arginine administration reverses this retention, leading to IGF-1 secretion. These data describe a novel IGF-1 secretion control system in the endoplasmic reticulum.

Keywords: Arginine; GH; IGF-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Hep G2 Cells
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Tumor Cells, Cultured

Substances

  • IGF1 protein, human
  • Insulin-Like Growth Factor I
  • Arginine