Inhibition of insulin secretion by interleukin-1 beta and tumour necrosis factor-alpha via an L-arginine-dependent nitric oxide generating mechanism

FEBS Lett. 1990 Dec 10;276(1-2):42-4. doi: 10.1016/0014-5793(90)80502-a.


Inhibition of glucose-induced insulin secretion by interleukin-1 beta (IL-1 beta), or IL-1 beta plus tumour necrosis factor-alpha (TNF-alpha), was less marked when rat islets of Langerhans were cultured for 12 h with these cytokines in L-arginine-free medium as opposed to medium containing L-arginine (1 mM). Inhibition of secretion by IL-1 beta was further alleviated when islets were maintained in L-arginine-free medium supplemented with N-omega-nitro-L-arginine methyl ester (NAME), while synergism between IL-1 beta plus TNF-alpha was completely abolished. Tissue culture medium nitrite levels were raised in islets treated with IL-1 beta or TNF-alpha (48 h). Cytokine-stimulated nitrite production was not observed in islets cultured with NAME (1 mM). In conclusion, an L-arginine-dependent nitric oxide generating mechanism is involved in the inhibition of insulin secretion by IL-1 beta, and accounts for the phenomenon of synergism between IL-1 beta and TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / metabolism
  • Arginine / pharmacology*
  • Cells, Cultured
  • Insulin / metabolism*
  • Insulin Antagonists
  • Insulin Secretion
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Kinetics
  • Nitric Oxide / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Insulin
  • Insulin Antagonists
  • Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Arginine