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

ABSTRACT

SIGNIFICANCE: Cytokines released in and around pancreatic islets during islet inflammation are believed to contribute to impaired ß cell function and ß cell death during the development of diabetes. Nitric oxide, produced by ß cells in response to cytokine exposure, controls many of the responses of ß cells during islet inflammation. Recent Advances Although nitric oxide has been shown to inhibit insulin secretion and oxidative metabolism and induce DNA damage in ß 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 ß cells. CRITICAL ISSUES Does nitric oxide mediate cytokine-induced ß cell damage, or is nitric oxide produced by ß cells in response to cytokines to protect ß cells from damage? FUTURE DIRECTIONS ß 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 ß cell mass during diabetes development.