Does nitric oxide mediate autoimmune destruction of beta-cells? Possible therapeutic interventions in IDDM.

摘要: Cytokines have been implicated as immunological effector molecules that induce dysfunction and destruction of the pancreatic beta-cell. The mechanisms cytokine action on beta-cell are unknown; however, nitric oxide, resulting from cytokine-induced expression oxide synthase, has cellular molecule mediating dysfunction. Nitric is a free radical targets intracellular iron-containing enzymes, which results in loss their function. IL-1 beta induces formation isolated rat islets insulinoma cell line, Rin-m5F. NMMA NAME, both inhibitors completely protect deleterious effects beta. These competitive nature inhibit cytokine-inducible constitutive isoforms synthase with nearly identical kinetics. This may preclude use therapeutic agents because increases blood pressure result inhibition activity. Aminoguanidine, an inhibitor nonenzymatic glycosylation extracellular constituents associated diabetic complications, recently reported to synthase. Aminoguanidine approximately 40-fold more effective inhibiting inducible isoform suggesting aminoguanidine or analogues serve potential block diseases production by In vivo administration TNF shown anti-diabetogenic NOD mouse. effect cytokines appears conflict evidence mediate dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)