Nrf2: The Master and Captain of Beta Cell Fate

Trends Endocrinol Metab. 2021 Jan;32(1):7-19. doi: 10.1016/j.tem.2020.11.002. Epub 2020 Nov 23.

Abstract

Prolonged hyperglycemia is toxic to pancreatic β cells, generating excessive reactive oxygen species, defective glucose-stimulated insulin secretion, decreased insulin production, and eventually β cell death and diabetes. Nrf2 is a master regulator of cellular responses to counteract dangerous levels of oxidative stress. Maintenance of β cell mass depends on Nrf2 to promote the survival, function, and proliferation of β cells. Indeed, Nrf2 activation decreases inflammation, increases insulin sensitivity, reduces body weight, and preserves β cell mass. Therefore, numerous pharmacological activators of Nrf2 are being tested in clinical trials for the treatment of diabetes and diabetic complications. Modulating Nrf2 activity in β cells is a promising therapeutic approach for the treatment of diabetes.

Keywords: Nrf2; diabetes; metabolic stress; oxidative stress; pancreatic beta cell; proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Proliferation / physiology
  • Humans
  • Insulin Secretion / genetics
  • Insulin Secretion / physiology
  • Insulin-Secreting Cells / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / genetics
  • Oxidative Stress / physiology
  • Reactive Oxygen Species / metabolism
  • Stress, Physiological / physiology

Substances

  • NF-E2-Related Factor 2
  • Reactive Oxygen Species