NDLI: Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans.

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Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans.

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Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lancaster, J. R. Corbett, J. A. Sweetland, M. A. Mcdaniel, M. L. Wang, J. L.
Description	Author Affiliation: Corbett JA ( Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.);
Abstract	Cytokines have been implicated as immunological effector molecules that mediate beta cell destruction associated with insulin-dependent diabetes mellitus. In this report we demonstrate that the cytokine combination of human recombinant interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) induces the formation of nitric oxide by human islets. This combination of cytokines stimulates both the formation of the nitric oxide derivative, nitrite, and the accumulation of cGMP by human islets. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine prevents formation of both cGMP and nitrite. IL-1 beta and IFN-gamma are sufficient to induce nitric oxide formation by human islets, whereas TNF-alpha potentiates nitrite production. This combination of cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) also influences insulin secretion by human islets. Pretreatment of human islets with low concentrations of this cytokine combination (IL-1 beta at 15 units/ml, 0.7 nM TNF-alpha, and IFN-gamma at 150 units/ml) appears to slightly stimulate insulin secretion. Higher concentrations (IL-1 beta at 75 units/ml, 3.5 nM TNF-alpha, and IFN-gamma at 750 units/ml) inhibit insulin secretion from human islets, and the inhibitory effect is prevented by NG-monomethyl-L-arginine. This higher concentration of cytokines also induces the formation of an electron paramagnetic resonance-detectable g = 2.04 axial feature by human islets that is characteristic of the formation of an iron-dithio-dinitrosyl complex. The formation of this complex is prevented by NG-monomethyl-L-arginine, thus confirming that this cytokine combination induces the formation of nitric oxide by human islets. These results indicate that nitric oxide mediates the inhibitory effects of cytokines on glucose-stimulated insulin secretion by human islets and suggest that nitric oxide may participate in beta-cell dysfunction associated with insulin-dependent diabetes mellitus.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Insulin Secretion Interferon-gamma Pharmacology Interleukin-1 Islets Of Langerhans Nitric Oxide Metabolism Tumor Necrosis Factor-alpha Arginine Analogs & Derivatives Cyclic GMP Diabetes Mellitus, Type 1 Physiopathology Electron Spin Resonance Spectroscopy In Vitro Techniques Nitrites Recombinant Proteins Secretory Rate Drug Effects Omega-N-Methylarginine Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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