AIM: To analyze the different effects of clozapine and
risperidone on the intracellular calcium concentration ( Ca2+ i) in
β cells of isolated rat islets under low and high glucose, and preliminarily discuss the possible mechanism in affecting the secretion of insulin.METHODS: The experiment was carried out in the central laboratory of Medical School of Wuhan University from January to June 2005. Ten healthy SD rats of 6-8 weeks were put to death by cutting off the head, and the pancreas was collected in aseptic condition. Under low and high glucose, the isolated and cultured rat islets were treated with clozapine and
risperidone respectively, blank control group was also set, the changing law of Ca2+ i represented by
fluorescence intensity was measured by laser scanning confocal microscope after β cells were loaded with calcium sensitive fluorescent indicator Fluo-4/AM.RESULTS: All the 10 experimental animals were involved in the analysis of results. ①Under low and high glucose, the time changing curve of Ca2+ i fluorescence graph after treatment of 1 μmol/L clozapine and risperidone in the risperidone group was similar to that in the clozapine group, the peak value in the clozapine group was lower than that in the risperidone group, and the stable Ca2+ i fluorescence was obviously lower than the baseline level. ② Under low and high glucose, as compared with the blank control group, clozapine could decrease the Ca2+ i (22±4), (93±6), P < 0.01; (62±10), (94±5), P < 0.01 , but risperidone had no influence on Ca2+ i (91±7), (93±6), P > 0.05; (91±8), (94±5), P > 0.05 . CONCLUSION: Under low and high glucose, clozapine can both decrease the Ca2+ i, but risperidone has no influence on Ca2+ i. It is considered that the different affinity of clozapine and risperidone to 5-serotonin 1 receptor A may be one of the reasons for the different influence on the secretion of insulin. The disorder of glucose metabolism induced by clozapine and risperidone may be related to the defect of insulin secretion and insulin resistance.