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

Aging (Albany NY). 2019 Aug 12;11(15):5726-5743. doi: 10.18632/aging.102155. Epub 2019 Aug 12.

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.

Keywords: SKN-1/Nrf2; aging; glucose; hyperglycemia; reactive oxygen species (ROS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / genetics
  • Aging / metabolism
  • Animals
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Herbicides / antagonists & inhibitors
  • Herbicides / toxicity
  • Humans
  • Longevity / drug effects
  • Longevity / physiology*
  • Models, Biological
  • Oxidative Stress / drug effects
  • Paraquat / antagonists & inhibitors
  • Paraquat / toxicity
  • Reactive Oxygen Species / metabolism*
  • Species Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Herbicides
  • Reactive Oxygen Species
  • Transcription Factors
  • skn-1 protein, C elegans
  • Glucose
  • Paraquat