title: Dual effect of advanced glycation end products in pancreatic islet apoptosis.
abstract: BACKGROUND
  Loss of β-cell function hastens deterioration of metabolic control in type 2 diabetes patients. Besides amyloid deposit and glucolipotoxicity, advanced glycation end products (AGEs) acting through their receptors (RAGE) seem to contribute to this process by promoting islet apoptosis. In order to investigate the role of AGEs in β-cell deterioration, we evaluated the temporal and dose effects of AGE compounds on apoptosis rate, reactive oxygen species generation and expression of pro-apoptotic and anti-apoptotic genes in cultured islets.
  
  
  METHODS
  Rat pancreatic islets were exposed or not for 24, 48, 72 and 96 h to albumin modified by glycoaldehyde. Apoptosis, reactive oxygen species and superoxide content and NADPH oxidase activity were evaluated as well as RNA expression of the genes Ager (codes for RAGE), Bax, Bcl2 and Nfkb1.
  
  
  RESULTS
  In 24 and 48 h, glycoaldehyde elicited a decrease in apoptosis rate in comparison with the control condition concomitantly with a reduction in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In contrast, after 72 and 96 h, glycoaldehyde promoted an increase in apoptosis rate concomitantly with an increase in Bax/Bcl2 RNA ratio and in Nfkb1 RNA expression. In 24 h, glycoaldehyde elicited a decrease in the islet content of reactive oxygen species, whereas after 48 and 72 h, it promoted an opposite effect, increasing superoxide generation. The NADPH oxidase inhibitor VAS2870 attenuated superoxide production, implicating NADPH oxidase as an important source of reactive oxygen species in islets exposed to AGEs.
  
  
  CONCLUSIONS
  Albumin modified by glycoaldehyde exerted a dual effect in cultured pancreatic islets, being protective against apoptosis after short exposure but pro-apoptotic after prolonged exposure.
authors: Faculdade de Medicina da Universidade de São Paulo, Laboratório de Endocrinologia Celular e Molecular LIM-25, São Paulo, Brazil.
authors: Flavia
authors: F
authors: Costal
authors: Erika
authors: E
authors: Oliveira
authors: Alexandre
authors: A
authors: Raposo
authors: Adriana
authors: A
authors: Machado-Lima
authors: Elisa
authors: E
authors: Peixoto
authors: Letícia
authors: L
authors: Roma
authors: Laila
authors: L
authors: Santos
authors: José B
authors: JB
authors: Lopes Faria
authors: Angelo Rafael
authors: AR
authors: Carpinelli
authors: Daniel
authors: D
authors: Giannella-Neto
authors: Marisa
authors: M
authors: Passarelli
authors: Maria Lucia
authors: ML
authors: Correa-Giannella
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D049449:Luminescence; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019255:NADPH Oxidases / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; C494828:Bax protein, rat; D017127:Glycation End Products, Advanced; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D052002:NF-kappa B p50 Subunit; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051028:bcl-2-Associated X Protein; D013481:Superoxides; D019255:NADPH Oxidases; D005947:Glucose