A Role for Nitric Oxide and Other Inflammatory Mediators in Cytokine-Induced Pancreatic β-Cell Dysfunction and Destruction

Abstract

Insulin-dependent diabetes mellitus is an autoimmune disease characterized by the selective destruction of the pancreatic β-cell. The autoimmune response that is ultimately responsible for the destruction of the β-cell consists of a number of complex components. Cytokines released during this inflammatory reaction have been implicated as effector molecules which mediate β-cell destruction^1–3. Our studies have focused primarily in attempting to define the role of cytokines released by both T-lymphocytes and activated macrophages to produce deleterious effects directly on the β-cell during the initial inflammatory response associated with autoimmune diabetes. Our studies have described the ability of the cytokine, interleukin-1 (IL-1), to both inhibit insulin secretion from the β-cell and also to produce cytotoxic effects via the formation of the free radical nitric oxide (NO). Our more recent studies have revealed that the ability of cytokines such as IL-1 to produce nitric oxide by islets is also directly linked to the production of the proinflammatory prostaglandins and thromboxanes that may play an important role in the initial inflammatory response that is the hallmark of autoimmune diabetes.