NITRIC-OXIDE PRIMES PANCREATIC BETA-CELLS FOR FAS-MEDIATED DESTRUCTION IN INSULIN-DEPENDENT DIABETES-MELLITUS

Fas is an apoptosis-inducing surface receptor involved in controlling tissue homeostasis and function at multiple sites. Here we show that b eta cells from the pancreata of newly diagnosed insulin-dependent diab etes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to Fas Ligand-expressing T lym phocytes infiltrating the IDDM islets. Normal human pancreatic beta ce lls that do not constitutively express Fas, become strongly Fas positi ve after interleuken (IL)-1 beta exposure, and are then susceptible to Fas-mediated apoptosis. N-G-monomethyl-L-arginine, an inhibitor of ni tric oxide (NO) synthase, prevents IL-1 beta-induced Fas expression, w hereas the NO donors sodium nitroprusside and nitric oxide releasing c ompound (NOC)-18, induce functional Fas expression in normal pancreati c beta cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic beta cell damage in IDDM.