Abstract

The effect of acetylsalicylate on gluconeogenesis in isolated rat kidney tubules was investigated. It was found that acetylsalicylate, at a concentration of 2 mM, inhibited tthe formation of glucose from several potentially glucogenic substrates including 2-oxoglutarate, succinate and d-fructose. Addition of butyrate to the incubation medium partially reversed or, in the case of oxoglutarate, eliminated the inhibition. Acetylsalicylata also caused an increase in the respiratory rate of isolated tubules and brought about a decrease in the intracellular ATP level. The effects of acetylsalicylate on gluconeogenesis and respiration were almost identical to the effects of 2,4-dinitrophenol on these processes. It is proposed that, in isolated rat kidney tubules, the fall in the intracellular level of ATP, caused by acetylsalicylate, is a consequence of the uncoupling of respiratory chain phosphorylation. The decreased rate of gluconeogenesis is considered to be a response to the lowered ATP level.

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