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.
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