Nitric Oxide Primes Pancreatic β 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 β cells from the pancreata of newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients express Fas and show extensive apoptosis among those cells located in proximity to Fas ligand–expressing T lymphocytes infiltrating the IDDM islets. Normal human pancreatic β cells that do not constitutively express Fas, become strongly Fas positive after interleuken (IL)-1β exposure, and are then susceptible to Fas-mediated apoptosis. NG-monomethyl-l-arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-1β–induced Fas expression, whereas the NO donors sodium nitroprusside and nitric oxide releasing compound (NOC)-18, induce functional Fas expression in normal pancreatic β cells. These findings suggest that NO-mediated upregulation of Fas contributes to pancreatic β cell damage in IDDM.

• Publication year

  1997

• Venue

  Journal of Experimental Medicine

• Publication date

  1997-10-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.186.8.1193PMID 9334358PMCID 2199078
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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