title: Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan.
abstract: BACKGROUND
  Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied.
  
  
  RESULTS
  In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively.
  
  
  CONCLUSIONS
  Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4, thus giving further insight into the pathophysiology of diabetic complications.
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: michael.mendler@med.uni-heidelberg.de.
authors: Michael
authors: M
authors: Mendler
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors: Christin
authors: C
authors: Riedinger
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; 5(th) Medical Department, University Medical Center, University of Heidelberg, Mannheim, Germany.
authors: Andrea
authors: A
authors: Schlotterer
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors: Nadine
authors: N
authors: Volk
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
authors: Thomas
authors: T
authors: Fleming
authors: Institute for Diabetes and Cancer IDC, Helmholtz Center Munich, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany; Joint Heidelberg IDC Translational Diabetes Program, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD).
authors: Stephan
authors: S
authors: Herzig
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; Joint Heidelberg IDC Translational Diabetes Program, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; German Center for Diabetes Research (DZD).
authors: Peter P
authors: PP
authors: Nawroth
authors: Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; 5(th) Medical Department, University Medical Center, University of Heidelberg, Mannheim, Germany.
authors: Michael
authors: M
authors: Morcos
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D005947:Glucose / Q000506:poisoning*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008136:Longevity; D009154:Mutation; D000066829:Neuroprotection; D009994:Osmolar Concentration; D018384:Oxidative Stress; D036361:Peptide Hormones / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D029742:Caenorhabditis elegans Proteins; D017127:Glycation End Products, Advanced; C525653:Ins-7 protein, C elegans; D036361:Peptide Hormones; D017382:Reactive Oxygen Species; C525107:Sod-3 protein, C elegans; D013482:Superoxide Dismutase; D007791:Lactoylglutathione Lyase; D005947:Glucose
keywords: Diabetic neuropathy; Glycation/AGE; Insulin action; Longevity; Neuronal function; Oxidative stress/ROS