The importance of nitric oxide in the cytokine-induced inhibition of glucose formation by cultured hepatocytes incubated with insulin, dexamethasone, and glucagon

Archives of Biochemistry and Biophysics
E D Ceppi, M A Titheradge

Abstract

Culturing hepatocytes with a combination of tumor necrosis factor alpha, interferon gamma, and interleukin 1 beta plus lipopolysaccharide resulted in an induction of nitric oxide synthase and concomitant inhibition of both hepatic gluconeogenesis and glycogenolysis. The inhibition of gluconeogenesis was evident both under basal conditions and in cells stimulated acutely with glucagon. The stimulation of glycogen mobilization by glucagon was largely prevented by the presence of the cytokines. Chronic 24-h treatment of the cells with glucagon attenuated the cytokine response on both glucose output and NO formation in the dexamethasone-treated cells. This effect was antagonized by insulin. Inclusion of 1 mM NG-nitro-L-arginine methyl ester or 0.5 mM NG-monomethyl-L-arginine in the incubation abolished the increase in NO2- plus NO3- induced by the cytokine mixture and partially reversed the inhibitory effects on glucose mobilization in the presence of either insulin or glucagon, confirming the involvement of NO. In contrast the NO synthase inhibitors had little effect on either gluconeogenesis or glycogenolysis in the presence of dexamethasone alone, indicating that NO is only partially responsible for the inhibitory action of the ...Continue Reading

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Citations

Apr 27, 2007·Intensive Care Medicine·Gerd AlbusziesEberhard Barth
Sep 28, 2000·Cell Calcium·N Kraus-Friedmann
Apr 26, 2012·The Journal of Physical Chemistry. B·Sophie BernadJérôme Santolini
Jan 8, 2015·Journal of Evidence-based Complementary & Alternative Medicine·Siavash BabajafariArman Zargaran
Feb 3, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·B ChristA Nath
Oct 16, 2007·Molecular and Cellular Biochemistry·Jennifer WallingtonMichael Alan Titheradge
Mar 11, 2000·American Journal of Physiology. Endocrinology and Metabolism·M ShiotaA D Cherrington
May 13, 1999·Biochimica Et Biophysica Acta·M A Titheradge

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