title: n-3 Polyunsaturated fatty acids protect against pancreatic β-cell damage due to ER stress and prevent diabetes development.
abstract: METHODS
  In this study, we focus on the effects of n-3 polyunsaturated fatty acids (PUFAs) on tunicamycin-, streptozotocin-, or high fat diet (HFD)-induced β-cell damage and dysfunction.
  
  
  METHODS
  Pretreatment with n-3 PUFAs protected RINm5F cells and mouse islets against tunicamycin-induced β-cell damage through suppression of ER stress and apoptosis induction. This protective effect of n-3 PUFAs on β-cells was further demonstrated by the normalization of insulin secretion in response to glucose in tunicamycin-treated islets. In multiple low-dose streptozotocin-induced diabetes models, fat-1 mice, which endogenously synthesize n-3 PUFAs from n-6 PUFAs, were fully resistant to the development of diabetes, with normal islet morphology, high insulin immunoreactivity, and decreased apoptotic cells. In HFD-induced diabetes models, fat-1 mice also exhibited improved glucose tolerance and functional β-cell mass. In both diabetes models, we observed an attenuation of ER stress in fat-1 mice. Interestingly, n-3 PUFAs attenuated the nuclear translocation of lipogenic transcription factors sterol regulatory element-binding protein-1 (SREBP-1) and C/EBPβ, induced by tunicamycin or HFD, suggesting that n-3 PUFAs suppress ER stress via modulation of SREBP-1 and C/EBPβ.
  
  
  CONCLUSIONS
  Together, these results suggest that n-3 PUFAs block ER stress, thus protecting β cells against diabetogenic insult; therefore, dietary supplementation of n-3 PUFAs has therapeutic potential for the preservation of functional β-cell mass.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Song
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Ui-Jin
authors.initials: UJ
authors.lastname: Bae
authors.affiliation: Department of Anatomy, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin; D014415:Tunicamycin
chemical_list: D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D007328:Insulin; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014415:Tunicamycin; D013311:Streptozocin
keywords: Apoptosis; ER stress; High-fat diet; Streptozotocin; n-3 PUFAs