Further studies on the effects of 5-hydroxytryptophan on plasma glucose and insulin in the mouse

The effects of 5-hydroxytryptophan on plasma concentrations of glucose and immunoreactive insulin were examined in conscious mice. Blood samples were obtained after anaesthetizing the mice lightly with ether at the desired time. Large doses of L-5-hydroxytryptophan (5HTP) (200-400 mg/kg IV) produced a dose-dependent hypoglycaemic response in fasted mice (e.g. control 5.7 +/- 0.2 mmol/l, 5HTP 400 mg/kg 2.6 +/- 0.3 mmol/l). This response was preceded by a significant elevation in the plasma immunoreactive insulin concentration (e.g. control 6 +/- 2 mU/l; 5HTP 400 mg/kg 53 +/- 7 mU/l). Induction of diabetes with alloxan (80 mg/kg IV 72 h previously) prevented the hypoglycaemic effect of 5HTP. Alloxan diabetes abolished the hyperinsulinaemic response to 100 mg/kg of 5HTP and reduced by 66% the response to 400 mg/kg of 5HTP. In alloxan diabetic mice 5HTP produced a marked hyperglycaemic response (control 17.9 +/- 2.0 mmol/l; 5HTP 100 mg/kg 36.1 +/- 2.3 mmol/l). In normal mice pre-treated with nialamide, a monoamine oxidase inhibitor, much lower doses of 5 HTP (5-10 mg/kg) were required to produce hypoglycaemia. There was no detectable elevation in the plasma insulin concentration accompanying the hypoglycaemic response to smaller doses of 5HTP in nialamide treated mice. The hyperinsulinaemic and hypoglycaemic actions of 5HTP in normal mice were prevented completely by pretreatment with benserazide, an inhibitor of aromatic amino acid decarboxylase. 5-hydroxytryptamine did not modify the plasma glucose concentration in either normal or nialamide-treated animals. It is concluded that the hypoglycaemic response to 5HTP in normal mice is mediated at least partly through an elevation in the plasma insulin concentration, although it is likely that additional mechanisms are involved.