C-elegans as model for the study of high glucose-mediated life span reduction
. (2009) C-elegans as model for the study of high glucose-mediated life span reduction. Diabetes, Vol.58 (No.11). pp. 2450-2456. ISSN 0012-1797 Full text not available from this repository.
Official URL: http://dx.doi.org/10.2337/db09-0567
OBJECTIVE-Establishing Caenorhabditis elegans as a model for glucose toxicity-mediated life span reduction.
RESEARCH DESIGN AND METHODS-C. elegans were maintained to achieve glucose concentrations resembling the hyperglycemic conditions in diabetic patients. The effects of high glucose on life span, glyoxalase-1 activity, advanced glycation end products (AGEs), and reactive oxygen species (ROS) formation and on mitochondrial function were studied.
RESULTS-High glucose conditions reduced mean life span from 18.5 +/- 0.4 to 16.5 +/- 0.6 days and maximum life span from 25.9 +/- 0.4 to 23.2 +/- 0.4 days, independent of glucose effects on cuticle or bacterial metabolization of glucose. The formation of methylglyoxal-modified mitochondrial proteins and ROS was significantly increased by high glucose conditions and reduced by mitochondrial uncoupling and complex IIIQo inhibition. Overexpression of the methylglyoxal-detoxifying enzyme glyoxalase-1 attenuated the life-shortening effect of glucose by reducing AGE accumulation (by 65%) and ROS formation (by 50%) and restored mean (16.5 +/- 0.6 to 20.6 +/- 0.4 days) and maximum life span (23.2 +/- 0.4 to 27.7 +/- 2.3 days). In contrast, inhibition of glyoxalase-1 by RNAi further reduced mean (16.5 +/- 0.6 to 13.9 +/- 0.7 days) and maximum life span (23.2 +/- 0.4 to 20.3 +/- 1.1 days). The life span reduction by glyoxalase-1 inhibition was independent from the insulin signaling pathway because high glucose conditions also affected daf-2 knockdown animals in a similar manner.
CONCLUSIONS-C. elegans is a suitable model organism to study glucose toxicity, in which high glucose conditions limit the life span by increasing ROS formation and AGE modification of mitochondrial proteins in a daf-2 independent manner. Most importantly, glucose toxicity can be prevented by improving glyoxalase-l-dependent methylglyoxal detoxification or preventing mitochondrial dysfunction. Diabetes 58:2450-2456, 2009
|Item Type:||Journal Article|
|Subjects:||R Medicine > RC Internal medicine|
|Divisions:||Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
|Journal or Publication Title:||Diabetes|
|Publisher:||American Diabetes Association|
|Official Date:||November 2009|
|Number of Pages:||7|
|Page Range:||pp. 2450-2456|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Netzwerk Altersforschung (NAR), Hopp-Stiftung fur Alternsforschung, Juvenile Diabetes Research Foundation, Manfred Lautenschlager Stiftung|
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