title: Inhibition of insulin secretion by interleukin-1 beta and tumour necrosis factor-alpha via an L-arginine-dependent nitric oxide generating mechanism.
abstract: 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.
authors: Department of Biochemistry, University of Sussex, Brighton, UK.
authors: C
authors: C
authors: Southern
authors: D
authors: D
authors: Schulster
authors: I C
authors: IC
authors: Green
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D007328:Insulin; D007329:Insulin Antagonists; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D001120:Arginine