title: Palmitic acid-rich diet suppresses glucose-stimulated insulin secretion (GSIS) and induces endoplasmic reticulum (ER) stress in pancreatic islets in mice.
abstract: The objective was to clarify whether dietary palmitic acid supplementation affects glucose-stimulated insulin secretion (GSIS) and the endoplasmic reticulum (ER) stress pathway in pancreatic islets in mice. Eight-week-old male C57BL/6J mice were randomly divided into three treatment diet groups: control diet, palmitic acid-supplemented diet (PAL) and oleic acid-supplemented diet (OLE). After 2 weeks of treatment, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were performed. GSIS was assessed by pancreatic perfusion in situ with basal (100 mg/dL) glucose followed by a high (300 mg/dL) glucose concentration. We measured mRNA levels of ER stress markers such as C/EBP homologous protein (CHOP), immunoglobulin heavy-chain binding protein (BIP) and X-box binding protein (XBP)-1 using real-time polymerase chain reaction (PCR) analyses in isolated islets. Immunohistochemical staining was also performed. Mice fed PAL showed significantly decreased glucose tolerance (p < 0.05). In the perfusion study, GSIS was significantly suppressed in the PAL group (p < 0.05). Semi-quantitative RT-PCR revealed that islet CHOP, BIP, and XBP-1 mRNA expression were significantly increased in the PAL group (p < 0.05). TUNEL-positive β-cells were not detected in all groups. Dietary palmitic acid-supplementation for 2 weeks might suppress GSIS and induce ER stress in pancreatic islets in mice, in the early stage of lipotoxicity.
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Takumi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .|b Institute for Integrated Sports Medicine, School of Medicine, Keio University , Tokyo , Japan , and.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kawai
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hirose
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kurosawa
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Chikako
authors.initials: C
authors.lastname: Fujii
authors.affiliation: c Institute for Advanced Medical Research, School of Medicine, Keio University , Tokyo , Japan.
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Fujita
authors.affiliation: c Institute for Advanced Medical Research, School of Medicine, Keio University , Tokyo , Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Seto
authors.affiliation: b Institute for Integrated Sports Medicine, School of Medicine, Keio University , Tokyo , Japan , and.
authors.forename: Hideo
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: a Department of Internal Medicine , School of Medicine, Keio University , Tokyo , Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid / Q000494:pharmacology*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D019308:Palmitic Acid; D005947:Glucose
keywords: Dietary palmitic acid; ER stress; lipotoxicity; β-cell