Effect of multiple cytokines plus bacterial endotoxin on glucose and nitric oxide production by cultured hepatocytes

Ceppi, E D, Smith, F S and Titheradge, M A (1996) Effect of multiple cytokines plus bacterial endotoxin on glucose and nitric oxide production by cultured hepatocytes. Biochemical Journal, 317 (2). pp. 503-507. ISSN 02646021

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Abstract

Treatment of cultured hepatocytes with a combination of cytokines, including tumour necrosis factor-a, interferon-¿ and interleukin-1ß, plus lipopolysaccharide resulted in a time-dependent induction of nitric oxide (NO) synthase (as measured by NO2- + NO3- production) and inhibition of hepatic gluconeogenesis and glycogen breakdown. The inhibition of glucose release was comparable with that observed following treatment of rats with lipopolysaccharide or treatment of isolated hepatocytes with artificial NO donors. In addition, this effect was also evident with all substrates tested that enter the gluconeogenic pathway below the level of phosphoenolpyruvate carboxykinase, suggesting that this combination of cytokines may underlie the inhibition of gluconeogenesis observed in endotoxic shock. The maximal inhibition of glucose output required the presence of all the cytokines plus lipopolysaccharide, whereas the induction of NO synthase was independent of the lipopolysaccharide when the cytokines were employed. Inclusion of interferon-¿ was essential to obtain a maximal response for either parameter. Inclusion of 1 mM N(G)-monomethyl-L-arginine in the incubation abolished the increase in NO2- + NO3- observed with the complete cytokine mixture and various combinations; however, it failed to prevent the inhibition in glucose output, indicating that mechanisms other than NO underlie the cytokine-induced inhibition of glucose release

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Michael Titheradge
Date Deposited: 06 Feb 2012 20:37
Last Modified: 22 Mar 2012 14:27
URI: http://sro.sussex.ac.uk/id/eprint/27056
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