Regulation of NOX-1 expression in beta cells: a positive feedback loop involving the Src-kinase signaling pathway

Mol Cell Endocrinol. 2013 Apr 30;369(1-2):35-41. doi: 10.1016/j.mce.2013.01.011. Epub 2013 Feb 11.


NADPH oxidase-1 (NOX-1) is upregulated in beta cells in response to pro-inflammatory cytokines. Inhibition of NADPH oxidase activity blocked stimulated NOX-1 expression (p<0.05). Regulation of NOX-1 expression in beta cells followed modulation of cellular reactive oxygen species (ROS); pro-oxidants increased NOX-1 (p<0.001) and anti-oxidants decreased NOX-1 (p<0.05). Activation of Src-kinase followed ROS elevation. Inhibition of Src-kinase decreased NOX-1 expression (p<0.01). Beta cell dysfunction, measured by elevated MCP-1 expression, loss of glucose-sensitive insulin secretion or cell death, was induced by pro-inflammatory cytokine stimulation. Importantly, inhibition of Src-kinase or NOX-1 preserved beta cell function and survival. Collectively, these data indicate that expression of NOX-1 in beta cells is regulated in a feed-forward loop mediated by ROS and Src-kinase. Uncoupling of this feed-forward activation could provide new approaches to preserve and protect beta cells in diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Cell Line
  • Cell Survival
  • Feedback, Physiological
  • Gene Expression Regulation
  • Humans
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / enzymology*
  • NADH, NADPH Oxidoreductases / metabolism*
  • NADPH Oxidase 1
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / metabolism*


  • Reactive Oxygen Species
  • NADH, NADPH Oxidoreductases
  • NADPH Oxidase 1
  • src-Family Kinases