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

• Published in: FEBS letters Vol. 276; no. 1; pp. 42 - 44
• Main Authors: Southern, C., Schulster, D., Green, I.C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.12.1990; Elsevier
• Subjects: Animals; Arginine - metabolism; Arginine - pharmacology; Biological and medical sciences; Cell physiology; Cells, Cultured; Fundamental and applied biological sciences. Psychology; Insulin - metabolism; Insulin Antagonists; Insulin Secretion; Interleukin-1 - pharmacology; Interleukin-1β; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Kinetics; L-Arginine; Molecular and cellular biology; Nitric oxide; Nitric Oxide - metabolism; Rat; Rats; Rats, Inbred Strains; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; Tumor Necrosis Factor-alpha - pharmacology; Tumour necrosis factor-α; L-Arginine; Tumour necrosis factor-α; Rat; Interleukin-1β; Nitric oxide; Insulin secretion; Secretion; Rodentia; Cytokine; Langerhans islet; Interleukin 1β; Biosynthesis; Insulin; Protein hormone; Vertebrata; Mammalia; Arginine; Tumor necrosis factor; Aminoacid; Nitrogen monoxide; Inhibition; Mechanism of action
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)80502-A

Inhibition of glucose-induced insulin secretion by interleukin-1β (IL-1β), or IL-1β plus tumour necrosis factor-α (TNF-α), 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-1β was further alleviated when islets were maintained in L-arginine-free medium supplemented with N-ω-nitro-L-arginine methyl ester (NAME), while synergism between IL-1β plus TNF-α was completely abolished. Tissue culture medium nitrite levels were raised in islets treated with IL-1β or TNF-α (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-1β, and accounts for the phenomenon of synergism between IL-1β and TNF-α.