Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species

Nava Bashan, Julia Kovsan, Ilana Kachko, Hilla Ovadia, Assaf Rudich

Research output: Contribution to journalReview articlepeer-review

444 Scopus citations


Regulated production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) adequately balanced by antioxidant systems is a prerequisite for the participation of these active substances in physiological processes, including insulin action. Yet, increasing evidence implicates ROS and RNS as negative regulators of insulin signaling, rendering them putative mediators in the development of insulin resistance, a common endocrine abnormality that accompanies obesity and is a risk factor of type 2 diabetes. This review deals with this dual, seemingly contradictory, function of ROS and RNS in regulating insulin action: the major processes for ROS and RNS generation and detoxification are presented, and a critical review of the evidence that they participate in the positive and negative regulation of insulin action is provided. The cellular and molecular mechanisms by which ROS and RNS are thought to participate in normal insulin action and in the induction of insulin resistance are then described. Finally, we explore the potential usefulness and the challenges in modulating the oxidant-antioxidant balance as a potentially promising, but currently disappointing, means of improving insulin action in insulin resistance-associated conditions, leading causes of human morbidity and mortality of our era.

Original languageEnglish
Pages (from-to)27-71
Number of pages45
JournalPhysiological Reviews
Issue number1
StatePublished - 1 Jan 2009

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)


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