NRF2 is required for neonatal mouse beta cell growth by maintaining redox balance and promoting mitochondrial biogenesis and function

LONP1 regulation of mitochondrial protein folding provides insight into beta cell failure in type 2 diabetes

“…62 Historically, β-cells have been reported to have low anti-oxidant capacity, which sensitizes them to oxidative damage, although more recent work has challenged this belief. 63, 64 Thus, we wished to determine if the generation of oxidative stress and DNA damage may be a driver of β-cell apoptosis in β-LonP1 KO mice. We evaluated changes in ROS between islets of 6-week-old control and β-LonP1 KO mice by flow cytometry, observing an increase in ROS levels in β-LonP1 KO islets (Figure 4A).…”

Inhibition of glycogen synthase kinase-3 enhances NRF2 protein stability, nuclear localisation and target gene transcription in pancreatic beta cells

“…However, previous work has identified key roles for NRF2 in beta cell proliferation [ 52 , 53 ] and polymorphisms in NFE2L2 , the NRF2-encoding gene, and pathway have been associated with diabetes risk [ [54] , [55] , [56] ]. Most recently, NRF2 levels were found to increase during beta cell proliferation in neonatal pancreas and to be required for proliferation, survival and beta cell mass expansion in early life, through its influence on mitochondrial ATP synthesis [ 53 ]. This implies that agents that enhance NRF2 function in beta cells could combat obesity-driven metabolic stress and protect the beta cell pool.…”