Intestinal bile acid composition modulates prohormone convertase 1β (PC1/3) expression and consequent GLP-1 production in male mice

Kohkichi Morimoto, Mitsuhiro Watanabe, Taichi Sugizaki, Junichiro Irie, Hiroshi Itoh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Besides an established medication for hypercholesterolemia, bile acid binding resins (BABRs) present antidiabetic effects. Although the mechanisms underlying these effects are still enigmatic, glucagon-like peptide-1 (GLP-1) appearstobe involved.Inadditiontoafew reported mechanisms, we propose prohormone convertase 1β (PC1β), an essential enzyme of GLP-1 production, as a potent molecule in the GLP-1 release induced by BABRs. In our study, the BABR colestimide leads to a bile acid-specific G protein-coupled receptor TGR5-dependent induction of PC1/3; gene expression. Here, we focused on the alteration of intestinal bile acid composition and consequent increase of total TGR5 agonistic activity to explain the TGR5 activation. Furthermore, we demonstrate that nuclear factor of activated T cells mediates the TGR5-triggered PC1/3 gene expression. Altogether, our data indicate that the TGR5-dependent intestinal PC1/3 gene expression supports the BABR-stimulated GLP-1 release. We also propose a combination of BABR and dipeptidyl peptidase-4 inhibitor in the context of GLP-1-based antidiabetic therapy.

Original languageEnglish
Pages (from-to)1071-1081
Number of pages11
JournalEndocrinology
Volume157
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

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Proprotein Convertase 1
Glucagon-Like Peptide 1
Bile Acids and Salts
Gene Expression
Hypoglycemic Agents
Dipeptidyl-Peptidase IV Inhibitors
NFATC Transcription Factors
G-Protein-Coupled Receptors
Hypercholesterolemia

ASJC Scopus subject areas

  • Endocrinology

Cite this

Intestinal bile acid composition modulates prohormone convertase 1β (PC1/3) expression and consequent GLP-1 production in male mice. / Morimoto, Kohkichi; Watanabe, Mitsuhiro; Sugizaki, Taichi; Irie, Junichiro; Itoh, Hiroshi.

In: Endocrinology, Vol. 157, No. 3, 01.03.2016, p. 1071-1081.

Research output: Contribution to journalArticle

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