title: Attenuation of streptozotocin-induced pancreatic beta cell death in transgenic fat-1 mice via autophagy activation.
abstract: BACKGROUND
  The incidence of diabetes has rapidly increased due to changes in eating habits. Inflammatory factors and beta (β) cell dysfunction due to high-fat diets aggravate chronic diseases and their complications. However, omega-3 dietary fats have anti-inflammatory effects, and the involvement of autophagy in the etiology of diabetes has been reported. Therefore, we examined the protective effects of autophagy on diabetes using fat-1 transgenic mice with omega-3 self-synthesis capability.
  
  
  METHODS
  Streptozotocin (STZ) administration induced β cell dysfunction in mice; blood glucose levels and water consumption were subsequently measured. Using hematoxylin and eosin (H&E) and Masson's trichrome staining, we quantitatively assessed STZ-induced changes in the number, mass, and fibrosis of pancreatic islets in fat-1 and control mice. We identified the microtubule-associated protein 1A/1B light chain 3-immunoreactive puncta in β cells and quantified p62 levels in the pancreas of fat-1 and control mice.
  
  
  RESULTS
  STZ-induced diabetic phenotypes, including hyperglycemia and polydipsia, were attenuated in fat-1 mice. Histological determination using H&E and Masson's trichrome staining revealed the protective effects of the fat-1 mutation on cell death and the scarring of pancreatic islets after STZ injection. In the β cells of control mice, autophagy was abruptly activated after STZ treatment. Basal autophagy levels were elevated in fat-1 mice β cells, and this persisted after STZ treatment. Together with autophagosome detection, these results revealed that n-3 PUFA enrichment might partly prevent the STZ-related pancreatic islet damage by upregulating the basal activity of autophagy and improving autophagic flux disturbance.
  
  
  CONCLUSIONS
  Fat-1 transgenic mice with a n-3 PUFA self-synthesis capability exert protective effects against STZ-induced β cell death by activating autophagy in β cells.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea.|Myunggok Research Institute, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Won Min
authors.initials: WM
authors.lastname: Hwang
authors.affiliation: Myunggok Research Institute, College of Medicine, Konyang University, Daejeon, Korea.|Department of Anatomy, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Bak
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Hong
authors.affiliation: Myunggok Research Institute, College of Medicine, Konyang University, Daejeon, Korea.|Department of Anatomy, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Seung Yun
authors.initials: SY
authors.lastname: Han
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Keun Young
authors.initials: KY
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Chungnam National University, Daejeon, Korea.|Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
authors.affiliation: Myunggok Research Institute, College of Medicine, Konyang University, Daejeon, Korea.|Division of Endocrinology, Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, Korea. mdldm@hanmail.net.
authors.forename: Dong Mee
authors.initials: DM
authors.lastname: Lim
keywords: Omega 3 fatty; beta cell; fat-1 transgenic mice 