Journal
JOURNAL OF DIABETES AND ITS COMPLICATIONS
Volume 31, Issue 2, Pages 304-310Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jdiacomp.2016.09.014
Keywords
Insulin action; Diabetic neuropathy; Glycation/AGE; Oxidative stress/ROS; Longevity; Neuronal function
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Funding
- German Research Foundation (DFG) [NA-137, SFB1118, TP C06, SFB1158, TP A03]
- German Center for Diabetes Research (DZD)
- DFG research training group [(GRK) 1874]
- Dietmar-Hopp-Foundation
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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. (C) 2017 Elsevier Inc. All rights reserved.
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