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

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.

Author information

1
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.
2
Department of Medicine 1 and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.
3
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.
4
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).
5
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).

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.

KEYWORDS:

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

PMID:
27776915
DOI:
10.1016/j.jdiacomp.2016.09.014
[Indexed for MEDLINE]

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