Influence of risperidone, clozapine and metabolites of clozapine on insulin secretion function of rat islets cultured in vitro
- VernacularTitle:体外培养大鼠胰岛分泌功能与利培酮和氯氮平及其代谢产物的干预效应
- Author:
Gaohua WANG
;
Huiling WANG
;
Yuan ZHOU
;
Xiaoping WANG
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(30):212-213
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Among atypical antipsychotic drugs (AAPDs), clozapine has the greatest effect on glucose metabolism, while risperidone, between clozapine, olanzapine and traditional antipsychotics, affects glucose metabolism less severely than clozapine.OBJECTIVE: To investigate the path through which the most commonly used AAPDs influence glucose metabolism by comparing the effects of risperidone, clozapine, and the metabolites of clozapine, desmethylclozapine (DCLO) and clozapine N-oxide (CNO), on insulin secretion in vitro.DESIGN: A completely randomized controlled design.SETTING: Center of Public Health of People's Hospital, Wuhan University.MATERIALS: The experiment was conducted in the Experiment Center of Stomatology Hospital, Wuhan University, from September 2003 to January 2004. Three healthy male Wistar rats of clean grade were used.bovine serum albumin and 3.3 mmoL/L glucose was added into each well (1 mL) for preincubation for 30 minutes. Then the supernatants were removed. Six wells were set as one group, and there were five groups altogether, namely, control group, risperidone group, clozapine group, DCLO group, and CNO group. All the groups were added with 1g/L dimethyl sulphoxide (DMSO), 3.3 mmol/L or 16.7 mmol/L glucose per hole (1 mL).Rrisperidone group, clozapine group, DCLO group, and CNO group were also added with 1 μmol/L risperidone, clozapine, DCLO, or CNO, respectively. For each group, three wells were incubated for another 1 hour, and the other three wells were incubated for 4 hours. Supernatants were collected and stored at -20 ℃ in the refrigerator. The experiment was repeated for three times. The level of insulin in the supernatants before and after study were expressed as the median (M) and quartile (P25, P75). Mann-Whitney test was used for data comparison.MAIN OUTCOME MEASURES: The level of insulin in the supernatants in the 5 groups.tion (GSIS) was significantly higher than that of basal insulin secretion, either 1 hour or 4 hours after incubation [1.91(1.68-2.62), 2.21(1.59-3.05) μU/IEQ;1.05(0.71-1.15), 1.65(1.16-1.84) μU/IEQ, P ＜ 0.05], which suggested that ferences in the level of basal insulin secretion and GSIS in risperidone group and CNO group were not significant either 1 hour or 4 hours after incubation. The level of basal insulin secretion of clozapine group after 4-hour incubation was lower than that of control group [1.65 (1.16-1.84),1.08 (0.88-1.20) μU/IEQ, P ＜ 0.05]. The level of GSIS in DCLO group was significantly lower either after 1-hour or 4-hour incubation [1.15(0.84-1.32), 1.91(1.68-2.62) μU/IEQ;1.08 (0.62 -1.33), 2.21(1.59-3.05) μU/IEQ, P ＜ 0.05,0.01].CONCLUSION: Clozapine affects basal insulin secretion, and its metabolite DCLO inhibits glucose-stimulated insulin secretion in vitro.Risperidone does not cause impairment in insulin secretion.
