Glucagon-like peptide-1 production in the GLUTag cell line is impaired by free fatty acids via endoplasmic reticulum stress

Hiroto Hayashi, Ren Yamada, Siddhartha Shankar Das, Taiki Sato, Aki Takahashi, Masahiro Hiratsuka, Noriyasu Hirasawa

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Objects Glucagon-like peptide-1 (GLP-1) is secreted from intestinal L cells, enhances glucose-stimulated insulin secretion, and protects pancreas beta cells. However, few studies have examined hypernutrition stress in L cells and its effects on their function. Here, we demonstrated that a high-fat diet reduced glucose-stimulated secretion of GLP-1 and induced expression of an endoplasmic reticulum (ER) stress markers in the intestine of a diet-induced obesity mouse model. Methods To clarify whether ER stress in L cells caused the attenuation of GLP-1 secretion, we treated the mouse intestinal L cell line, GLUTag cells with palmitate or oleate. Results Palmitate, but not oleate caused ER stress and decreased the protein levels of prohormone convertase 1/3 (PC1/3), an essential enzyme in GLP-1 production. The same phenomena were observed in GLUTag cells treated with in ER stress inducer, thapsigargin. Moreover, oleate improved palmitate-induced ER stress, reduced protein and activity levels of PC1/3, and attenuated GLP-1 secretion from GLUTag cells. Conclusions/ Interpretation These results suggest that the intake of abundant saturated fatty acids induces ER stress in the intestine and decreases GLP-1 production.

Original languageEnglish
Pages (from-to)800-811
Number of pages12
JournalMetabolism: Clinical and Experimental
Volume63
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • ER stress
  • GLP-1
  • GLUTag
  • PC1/3

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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