Clozapine and olanzapine, but not conventional antipsychotics, increase insulin release in vitro.

This study was undertaken to examine the influence of conventional and atypical antipsychotics on insulin release in vitro, using isolated pancreatic islets and insulin-secreting INS-1 cells. The effect of the conventional antipsychotics haloperidol and zuclopenthixol, and the atypical agents clozapine and olanzapine in the concentration of 10(-6) M was investigated on basal and glucose-stimulated insulin release. Both clozapine and olanzapine increased basal insulin release, whereas zuclopenthixol inhibited glucose-stimulated release and haloperidol had no significant effect. In summary, clozapine and olanzapine, in contrast to conventional antipsychotics, increase basal insulin release. Interestingly, this stimulatory effect on insulin release in vitro may be supported by recent clinical findings, showing elevated insulin levels in patients being treated with clozapine or olanzapine.