Nitric oxide primes pancreatic β cells for Fas-mediated destruction in insulin-dependent diabetes mellitus

Giorgio Stassi, Ruggero De Maria, Giuliana Trucco, William Rudert, Roberto Testi, Aldo Galluzzo, Carla Giordano, Massimo Trucco

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

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)-β exposure, and are then susceptible to Fas-mediated apoptosis. N(G)-monomethyl-L- arginine, an inhibitor of nitric oxide (NO) synthase, prevents IL-β-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.

Original languageEnglish
Pages (from-to)1193-1200
Number of pages8
JournalJournal of Experimental Medicine
Volume186
Issue number8
DOIs
Publication statusPublished - Oct 20 1997

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Type 1 Diabetes Mellitus
Nitric Oxide
Apoptosis
Fas Ligand Protein
Nitric Oxide Donors
Nitroprusside
Nitric Oxide Synthase
Arginine
Pancreas
Homeostasis
Up-Regulation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Nitric oxide primes pancreatic β cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. / Stassi, Giorgio; De Maria, Ruggero; Trucco, Giuliana; Rudert, William; Testi, Roberto; Galluzzo, Aldo; Giordano, Carla; Trucco, Massimo.

In: Journal of Experimental Medicine, Vol. 186, No. 8, 20.10.1997, p. 1193-1200.

Research output: Contribution to journalArticle

Stassi, Giorgio ; De Maria, Ruggero ; Trucco, Giuliana ; Rudert, William ; Testi, Roberto ; Galluzzo, Aldo ; Giordano, Carla ; Trucco, Massimo. / Nitric oxide primes pancreatic β cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. In: Journal of Experimental Medicine. 1997 ; Vol. 186, No. 8. pp. 1193-1200.
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