Factors affecting tryptophan-induced hypoglycaemia in rats |
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Authors: | Peter Lloyd Stephen A. Smith Donald Stribling Christopher I. Pogson |
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Affiliation: | 1. Biological Laboratory, University of Kent, Canterbury CT2 7NJ, U.K.;2. Imperial Chemical Industries plc, Pharmaceuticals Division, Alderley Park, Macclesfield, Cheshire SK10 4TG, U.K. |
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Abstract: | The mechanisms whereby tryptophan administration leads to hypoglycaemia in some groups of rats but not others have been investigated. Animals insensitive to tryptophan are rendered responsive by adrenalectomy. This effect is reversed by steroid replacement. Turnover studies with [2-3H]glucose show that hypoglycaemia in sensitive animals is associated with a decrease in glucose synthesis. Tryptophan administration causes a marked and sustained increase in plasma glucagon concentrations in all animals. The locus of the inhibition of gluconeogenesis in tryptophan-sensitive animals is the reaction catalysed by phosphoenolpyruvate carboxykinase. The sensitivities to tryptophan of gluconeogenesis in isolated hepatocytes from normal and adrenalectomized animals were similar. Cells from chronically streptoxotocin-diabetic animals required higher concentrations of the amino acid for the same effect. These results are discussed in relation to previous discrepancies in the literature, and a unifying hypothesis for tryptophan-induced hypoglycaemia is proposed. |
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Keywords: | Present address: Nuffield Department of Clinical Biochemistry University of Oxford John Radcliffe Hospital Headington Oxford OX3 9DU U.K. (to whom correspondence should be addressed) |
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