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
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....
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| Main Authors: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
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| In: |
Journal of diabetes and its complications
Year: 2017, Volume: 31, Issue: 2, Pages: 304-310 |
| ISSN: | 1873-460X |
| DOI: | 10.1016/j.jdiacomp.2016.09.014 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.jdiacomp.2016.09.014 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1056872716306365 
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| Author Notes: | Michael Mendler, Christin Riedinger, Andrea Schlotterer, Nadine Volk, Thomas Fleming, Stephan Herzig, Peter P. Nawroth, Michael Morcos |
| Summary: | 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. |
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| Item Description: | Online 1 October 2016 Gesehen am 26.09.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1873-460X |
| DOI: | 10.1016/j.jdiacomp.2016.09.014 |