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Lack of Inhibition by l-Tryptophan or Quinolinate of Gluconeogenesis in Diabetic Rats

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      Administration of l-tryptophan to normal fed rats inhibits hepatic gluconeogenesis at the level of P-enolpyruvate formation but nonetheless causes a paradoxical increase in the assayable specific activity of P-enolpyruvate carboxykinase. Similar results obtain if livers isolated from normal rats are perfused with tryptophan, 3-hydroxyanthranilate or quinolinate.
      However, we find that no such inhibition of gluconeogenesis occurs in intact, fed, alloxan- or streptozotocin-diabetic rats following treatment with tryptophan or 3-hydroxyanthranilic acid, nor is there any increase in the already elevated assayable specific activity of P-enolpyruvate carboxykinase. Furthermore, perfusion of livers isolated from alloxan- or streptozotocin-diabetic rats with tryptophan, 3-hydroxyanthranilate or quinolinate does not produce a metabolite crossover between P-enolpyruvate and its precursors nor is there any significant enhancement of assayable specific activity of P-enolpyruvate carboxykinase. Additionally, perfusion of diabetic livers with tryptophan or quinolinate does not inhibit the conversion of radioactive lactate to glucose although such inhibition does occur in livers from normal rats.
      The results suggest that tryptophan and certain of its metabolites, including quinolinate, are unable to inhibit gluconeogenesis in diabetic rats under conditions known to cause such inhibition in normal rats.

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