title: Glucagon-like peptide-1 production in the GLUTag cell line is impaired by free fatty acids via endoplasmic reticulum stress.
abstract: OBJECTIVE
  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
  These results suggest that the intake of abundant saturated fatty acids induces ER stress in the intestine and decreases GLP-1 production.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Yamada
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Siddhartha Shankar
authors.initials: SS
authors.lastname: Das
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan. Electronic address: hirasawa@m.tohoku.ac.jp.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects* / Q000378:metabolism; D007739:L Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D019301:Oleic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D010168:Palmitates / Q000008:administration & dosage / Q000009:adverse effects*; D045664:Proprotein Convertase 1 / Q000037:antagonists & inhibitors*; D060888:Real-Time Polymerase Chain Reaction; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010168:Palmitates; D019301:Oleic Acid; D019284:Thapsigargin; D052216:Glucagon-Like Peptide 1; D045664:Proprotein Convertase 1
keywords: ER stress; GLP-1; GLUTag; PC1/3