Conserved roles of glucose in suppressing reactive oxygen species-induced cell death and animal survival

Abstract

Carbohydrate overconsumption increases blood glucose levels, which contributes to the development of various diseases including obesity and diabetes. It is generally believed that high glucose metabolism increases cellular reactive oxygen species (ROS) levels, damages insulin-secreting cells and leads to age-associated diabetic phenotypes. Here we find that in contrast, high glucose suppresses ROS production induced by paraquat in both mammalian cells and the round worm C. elegans . The role of glucose in suppressing ROS is further supported by glucose’s ability to alleviate paraquat’s toxicity on C. elegans development . Consistently, we find that the ROS-regulated transcription factor SKN-1 is inactivated by glucose. As a result, the ROS/SKN-1-dependent lifespan extension observed in paraquat-treated animals, mitochondrial respiration mutant isp-1 and germline-less mutant glp-1 are all suppressed by glucose. Our study reveals an unprecedented interaction of glucose with ROS, which could have significant impact on our current understanding of glucose- and ROS-related diseases.

High-glucose diets induce mitochondrial dysfunction in Caenorhabditis elegans

“…A similar downregulation of gcs-1 and gst-4 mRNA has been reported in glucose-fed worms, which was shown to be a consequence of the inhibition of the SKN-1-mediated immune response to the infection with Salmonella typhimurium [69]. Along the same lines, the SKN-1-mediated increase of expression of gcs-1 and gst-4 in response to Paraquat was suppressed in the presence of glucose [70]. It is interesting to note that the knockdown of some genes of the detoxification system increased the anoxia survival rate of glucose-treated worms or hyl-2 mutants [68].…”

The redox language in neurodegenerative diseases: oxidative post-translational modifications by hydrogen peroxide

“…For example, a study by Schulz et al 82 demonstrated that glucose deprivation increases OXPHOS and mtROS, and delays C. elegans aging. Similarly, a recent study by Wang et al 83 showed that lifespan extension conferred by the increased mtROS was diminished by glucose via reducing cellular ROS levels. Other studies echo this concept by identifying the increase in mtROS as a common aftermath of numerous conserved longevity-promoting interventions, thus originating the term “mitohormesis” 84 , 85 .…”

Scientific Challenges on Theory of Fat Burning by Exercise

“…Glucose and reactive oxygen species (ROS) also stimulate the adipogenic conversion from muscle-derived stem cells ( Aguiari et al, 2008 ). Both plasma glucose and ROS elevate with age and weight growth ( Ho et al, 2019 ; Wang et al, 2019 ). However, exercise training lowers plasma glucose ( Colberg et al, 2010 ) and ROS ( Vinetti et al, 2015 ) in animals and humans.…”