title: Stimulation of autophagy in the liver by lipopolysaccharide-induced systemic inflammation in a rat model of diabetes mellitus.
abstract: The dysregulated metabolism associated with diabetes mellitus (DM) impairs membrane trafficking events in the liver, including the process of autophagy, which is an essential ongoing cellular process that is highly regulated by nutrients, endocrine factors, and signaling pathways. High-mobility group box 1 (HMGB1) is a nuclear protein with a known role in systemic inflammation and the related various organ injuries. However, its relationship to autophagy is not well understood. The aim of this study was to investigate the effects of inflammation injury on autophagy in the liver in a rat model of DM. DM was induced in animals with streptozotocin, followed four weeks later by induction of inflammation by LPS injection. At 12 h after LPS administration, autophagy was assessed by immunohistochemistry and Western blot analysis of microtubule-associated protein light chain 3 (LC3)-II, as well as transmission electron microscopy. Expression of HMGB1 was also examined by immunohistochemistry and Western blot analysis. Western blot analysis of liver tissue revealed that levels of LC3-II and HMGB1 protein increased in DM rats subjected to LPS-induced inflammation compared with non-DM rats. Autophagy was particularly enhanced in DM rats. Thus, autophagy might be related to progression to organ injury in patients with DM, and inflammation in these patients might be associated with over-induction of autophagy and increased HMGB1 expression.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Oita University, Yufu, Oita, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Kudo
authors.forename: Jyunya
authors.initials: J
authors.lastname: Kusaka
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Oyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D024243:HMGB1 Protein / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D024243:HMGB1 Protein; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; C104200:Hbp1 protein, rat; C526109:Anxa3 protein, rat