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Updated: Jul 9, 2026

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
Published on: May 10, 2018
Effects of the atypical antipsychotic clozapine on insulin release in vitro
Kristina Melkersson1, Eva Jansson
1Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden. Kristina.Melkersson@ki.se
Objectives:
Treatment with the atypical antipsychotic clozapine is frequently associated with metabolic side-effects such as weight gain, lipid abnormalities and diabetes mellitus. Since insulin is a hormone that is involved in both the regulation of body weight, as well as in lipid metabolism and glucose regulation, an effect of clozapine on insulin secretion and/or on insulin action - at least in part - might explain its capability to induce these side-effects. The aim of this study was therefore to examine the influence of clozapine on insulin release in vitro.
Methods:
The effect of clozapine in three different concentrations, 10(-6), 10(-5) and 10(-4) M, was investigated on both basal (i.e. 3.3 mM glucose) and glucose-stimulated (i.e. 16.7 mM glucose) insulin release, using isolated rat islets of Langerhans.
Results:
The presence of clozapine in the concentrations of 10(-6), 10(-5) and 10(4 )M significantly increased basal insulin release compared to the control after 4 h (but not after 1 h) of incubation. As regards the glucose-stimulated insulin release, the presence of clozapine in the concentrations of 10(-5) and 10(-4) M, but not in that of 10(-6) M, significantly inhibited the glucose-stimulated insulin release compared to the control after both 1 and 4 h of incubation.
Conclusion:
This study demonstrates that the atypical antipsychotic clozapine exerts dual effects on insulin release in vitro, through stimulating basal insulin release and inhibiting glucose-stimulated insulin release. Both these effects of clozapine on insulin release may contribute to its disadvantage inducing metabolic side-effects.
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