Dual Role of Nitric Oxide in Regulating the Response of β Cells to DNA Damage.

SIGNIFICANCE: Cytokines released in and around pancreatic islets during islet inflammation are believed to contribute to impaired β cell function and β cell death during the development of diabetes. Nitric oxide, produced by β cells in response to cytokine exposure, controls many of the responses of β cells during islet inflammation. Recent Advances: Although nitric oxide has been shown to inhibit insulin secretion and oxidative metabolism and induce DNA damage in β cells, it also activates protective pathways that promote recovery of insulin secretion and oxidative metabolism and repair of damaged DNA. Recent studies have identified a novel role for nitric oxide in selectively regulating the DNA damage response in β cells. CRITICAL ISSUES: Does nitric oxide mediate cytokine-induced β cell damage, or is nitric oxide produced by β cells in response to cytokines to protect β cells from damage? FUTURE DIRECTIONS: β cells appear to be the only islet endocrine cell type capable of responding to proinflammatory cytokines with the production of nitric oxide, and these terminally differentiated cells have a limited capacity to regenerate. It is likely that there is a physiological purpose for this response, and understanding this could open new areas of study regarding the loss of functional β cell mass during diabetes development.