Kinetics of 5-hydroxytryptophan potentiation of glucose-induced insulin release

We have previously shown that L-5-hydroxytryptophan (L-5-HTP) potentiates glucose-induced insulin release in islets isolated from ob/ob-mice. In the present study, the kinetics of this effect were further studied. The combined effect of glucose and L-5-HTP was dependent on the concentration of both compounds. The threshold concentration for the potentiating effect of 5-HTP was on the order of 0.01-0.1 mmol/l, and the maximal effect was reached at 1-4 mmol/l extracellular concentration. L-5-HTP enhanced glucose-induced insulin release without changing the apparent Km for glucose (9.5-10 mmol/l). The effect of L-5-HTP increased with time for about 40 to 60 min and was reversibly reduced when either L-5-HTP was omitted or the glucose concentration was lowered. These findings support the view that L-5-HTP is a strong potentiator of glucose-induced insulin release.