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INHIBITION BY SALICYLATE OF GLUCONEOGENESIS IN THE ISOLATED PERFUSED RAT LIVER |
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| Authors: | H. F. Woods W. A. Stubbs G. Johnson K. G. M. M. Alberti |
| Affiliation: | Department of the Regius Professor of Medicine and Nuffield Department of Medicine, Radcliffe Infirmary, Oxford and Division of Pathology, Southampton General Hospital, Southampton |
| Abstract: | SUMMARY 1. Sodium salicylate has been used as a hypoglycaemic agent in the treatment of diabetic patients and severe hypoglycaemia has been reported in children treated with aspirin. The mechanism of this hypoglycaemic action has never been elucidated. 2. In the isolated perfused rat liver, salicylate inhibits gluconeogenesis from lactate, alanine and propionate. The degree of inhibition is related to salicylate concentration and occurs with 2 mM (30 mg/100 ml). 3. The inhibitory action probably results from the effect of salicylate on oxidative phosphorylation in that there was little or no inhibition of gluconeogenesis from precursors which do not have a high requirement for ATP in their metabolism to glucose. 4. In man, lactate and alanine are the main precursors of glucose, and the liver is the main site of gluconeogenesis. These results demonstrate a mechanism for salicylate induced hypoglycaemia in man, and in addition suggest that accumulation of lactate may account for the acidosis sometimes produced by overdosage with salicylate. |
| Keywords: | hypoglycaemia perfusion rat liver salicylates. |