2141-P: Nrf2 Mediates Glucose-Stimulated Beta-Cell Proliferation

Glucose catabolism drives adaptive beta cell mass expansion by promoting proliferation under conditions of increased insulin demand. Previously, we showed that induction of the antioxidant regulator, Nrf2, is required for glucose-stimulated β-cell proliferation, and that overexpression of Nrf2 stimulates human beta cell proliferation. Here we manipulate the Nrf2 pathway using pharmacological and genetic approaches to explore the link between glucose metabolism, Nrf2 activation and beta cell proliferation. Treatment of isolated mouse islets with either a Nrf2 inhibitor (brusatol) or Cre-recombinase deleted Nrf2, resulted in complete inhibition of glucose-stimulated proliferation (both n=3, p Disclosure S. Baumel-Alterzon: None. L.S. Katz: None. G. Brill: None. A. Garcia-Ocana: None. D. Scott: None. Funding American Diabetes Association (1-17-IBS-116 to D.S.); National Institutes of Health