What Mediates Interleukin 1-Induced Islet Dysfunction

WHAT MEDIATES INTERLEUKIN 1-INDUCED ISLET DYSFUNCTION  

Although oxygen radicals are destructive to islet cells, the inability of nicotinamide, Probucol, and other free radical scavengers to completely prevent cytokine mediated islet destruction suggests that other cytotoxic mechanisms may be involved in cytokine-induced islet-cell lysis. The possible interactions of superoxide with nitric oxide resulting in the generation of peroxynitrite and hydroxyl radicals may contribute to islet-cell lysis. The chemistry of these free radical interactions, and potential biological roles t)f these toxic radicals are reviewed in this book (see Chapter 1). 

MECHANISM OF NITRIC OXIDE-MEDIATED ISLET DYSFUNCTION AND DESTRUCTION 

How does nitric oxide mediate /8-cell dysfunction and destruction The observation of an IL-1/3-induced iron-dithio-dinitrosyl complex in islets suggests 

Interleukin 1-induced formation of iron-nitrosyl complexes by rat islets. Rat islets were incubated fot 18 hr in the presence or absence of 5 U/ml lL-1, 0.5 mM NMMA, or lL-1 and NMMA. The islets were isolated and the fotmation of nitric oxide was examined by EPR spectroscopy as described previously (Corbett et al., 1991a). IL-1 induces the formation of a g = 2.04 featute that is characteristic of the fotmation of iton-nittosyl complexes, and NMMA ptevents the formation of this axial g = 2.04 iton-nittosyl feature. Also shown is the simultaneous formation of nitrite by the same islets used for EPR spectroscopy. Repnxluced with permission from ]. Biol. Chem. (Corbett et al., 1991a), from the American Society for Biochemistry and Molecular Biology. 

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III. WHAT MEDIATES INTERLEUKIN 1-INDUCED ISLET DYSFUNCTION ... 

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