Glucocorticoids decrease the production of glucagon-like peptide-1 at the transcriptional level in intestinal L-cells

Taiki Sato, Hiroto Hayashi, Masahiro Hiratsuka, Noriyasu Hirasawa

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Glucocorticoids are widely used as anti-inflammatory or immunosuppressive drugs, but often induce hyperglycemia as a side effect. Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells and plays crucial roles in maintaining glucose homeostasis. However, the direct effects of glucocorticoids on the GLP-1 production pathway in L cells remain unclear. We investigated the effects of glucocorticoids on GLP-1 production in vitro and in vivo. In L cell lines, glucocorticoids decreased GLP-1 release and expression of the precursor, proglucagon, at protein and mRNA levels, which were inhibited by mifepristone. The administration of dexamethasone or budesonide to mice significantly decreased the mRNA expression of proglucagon in the ileum and partially decreased glucose-stimulated GLP-1 secretion. Compound A, a dissociated glucocorticoid receptor modulator, did not affect the expression of proglucagon in vitro. These results suggested that glucocorticoids directly reduced GLP-1 production at the transcriptional level in L cells through a glucocorticoid receptor dimerization-dependent mechanism.

Original languageEnglish
Pages (from-to)60-67
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume406
DOIs
Publication statusPublished - 2015 May 5

Keywords

  • Glucagon-like peptide-1
  • Glucocorticoids
  • Intestinal L-cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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