Low doses of tumour necrosis factor alpha and interleukin 1beta diminish hepatic gluconeogenesis from alanine in vivo.
Previous reports have attributed a stimulating action on hepatic gluconeogenesis to tumour necrosis factor alpha (TNFalpha) administered to rats at high doses (250 mug/kg). However, in adjuvant-induced arthritic rats, which present TNFalpha 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 TNFalpha and interleukin 1beta (IL1beta). TNFalpha and IL1beta at doses of up to 10 mug/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 TNFalpha and IL1beta, either alone or in combination, presented diminished gluconeogenesis. The degrees of inhibition caused by TNFalpha+IL1beta, TNFalpha and IL1beta were, respectively, 48.5, 38.8 and 30.4%. TNFalpha also diminished oxygen uptake. No action on urea and ammonia production was found. Possibly, both TNFalpha and IL1beta 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.
Kelmer-Bracht
Ana Maria
AM
Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil. adebracht@uol.com.br
Broetto-Biazon
Ana Carla
AC
de Sá-Nakanishi
Anacharis Babeto
AB
Ishii-Iwamoto
Emy Luiza
EL
Bracht
Adelar
A
D000409:Alanine / Q000378:metabolism*; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007262:Infusions, Intravenous; D053583:Interleukin-1beta / Q000008:administration & dosage*; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D014508:Urea / Q000378:metabolism
D004338:Drug Combinations; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D000641:Ammonia; D019289:Pyruvic Acid; D014508:Urea; D005947:Glucose; D000409:Alanine