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Low Doses of Tumour Necrosis Factor α and Interleukin 1β Diminish Hepatic Gluconeogenesis from Alanine in vivo
Author(s) -
KelmerBracht Ana Maria,
BroettoBiazon Ana Carla,
De SáNakanishi Anacharis Babeto,
IshiiIwamoto Emy Luiza,
Bracht Adelar
Publication year - 2006
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.pto_496.x
Subject(s) - gluconeogenesis , tumor necrosis factor alpha , medicine , endocrinology , chemistry , necrosis , biology , metabolism
Abstract: Previous reports have attributed a stimulating action on hepatic gluconeogenesis to tumour necrosis factor α (TNFα) administered to rats at high doses (250 μg/kg). However, in adjuvant‐induced arthritic rats, which present TNFα and other interleukins in the circulation, hepatic gluconeogenesis is diminished. The same occurs in some types of experimental cancer models as, for example, rats bearing the Walker‐256 tumour. The present work represents an attempt of reproducing in rats gluconeogenesis inhibition by interleukins using low instead of high doses of both TNFα and interleukin 1β (IL1β). TNFα and IL1β at doses of up to 10 μg/kg were given endovenously to rats and, after six hours, gluconeogenesis from alanine and several related parameters were evaluated in the isolated haemoglobin‐free perfused rat liver. Livers from rats injected with TNFα and IL1β, either alone or in combination, presented diminished gluconeogenesis. The degrees of inhibition caused by TNFα+IL1β, TNFα and IL1β were, respectively, 48.5, 38.8 and 30.4%. TNFα also diminished oxygen uptake. No action on urea and ammonia production was found. Possibly, both TNFα and IL1β contribute to the decreased rates of hepatic gluconeogenesis that were found in rats with arthritis, sepsis and some kinds of cancer, but not to the decreased rates of ureagenesis.