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

J Diabetes Complications. 2017 Feb;31(2):304-310. doi: 10.1016/j.jdiacomp.2016.09.014. Epub 2016 Oct 1.


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.

Keywords: Diabetic neuropathy; Glycation/AGE; Insulin action; Longevity; Neuronal function; Oxidative stress/ROS.

MeSH terms

  • Animals
  • Behavior, Animal
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / agonists
  • Caenorhabditis elegans Proteins / antagonists & inhibitors*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental*
  • Gene Knockdown Techniques
  • Gene Knockout Techniques
  • Glucose / poisoning*
  • Glycation End Products, Advanced / metabolism
  • Lactoylglutathione Lyase / antagonists & inhibitors
  • Lactoylglutathione Lyase / genetics
  • Lactoylglutathione Lyase / metabolism*
  • Longevity
  • Mutation
  • Neuroprotection
  • Osmolar Concentration
  • Oxidative Stress*
  • Peptide Hormones / agonists
  • Peptide Hormones / antagonists & inhibitors*
  • Peptide Hormones / genetics
  • Peptide Hormones / metabolism
  • RNA Interference
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / antagonists & inhibitors
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Survival Analysis


  • Caenorhabditis elegans Proteins
  • Glycation End Products, Advanced
  • Ins-7 protein, C elegans
  • Peptide Hormones
  • Reactive Oxygen Species
  • Sod-3 protein, C elegans
  • Superoxide Dismutase
  • Lactoylglutathione Lyase
  • Glucose