Mechanisms Research Of The Effects Of Clozapine On Blood Glucose In The Male C57BL/6 Mice

ObjectiveTo investigate the acute and chronic effects of the different dose of clozapine on fasting blood glucose, glucose tolerance, serum insulin, the gene expression of GLUT4, pancreatic β cell apoptosis in the male C57BL/6 mice. MethodsSixty-three male C57BL/6 mice were randomly divided into 3 groups, which administrated with distilled water, clozapine 4mg/kg, clozapine 20mg/kg. After administrated with clozapine by gastrogavage of 3 hours, 1 week, 4 weeks, the mice were given glucose tolerance test. The blood glucose values were measured at 0, 30, 60, 120 minute after glucose tolerance test. After collection the specimens, serum insulin, the gene expression of GLUT4, pancreatic (3 cell apoptosis were determined by RIA, RT-PCR and TUNEL respectively. Results1. 3 hours or 1 week after the administration, the fasting blood glucose, serum insulin and glucose AUC had no significant elevation (P > 0.05).2. 4 weeks after the administration, the fasting glucose increasedsignificantly (P < 0.01), the blood glucose of clozapine 20mg/kg increased significantly (P < 0.01) after the treatment with glucose (25% 2g/kg ip) 60 min, and serum insulin of clozapine 4mg/kg and clozapine 20mg/kg increased significantly (P < 0.05).3. The gene expression of GLUT4 had no significant decline 3 hours and 1 week after the administration. 4 weeks after the administration, the gene expression of GLUT4 of clozapine 4mg/kg and clozapine 20mg/kg decreased significantly (P < 0.01).4. The edge of the pancreatic islets of the control, clozapine 4mg/kg, clozapine 20mg/kg were clear and the islets cells showed propotional distribution. Exterior and interior secretory portion were distinct. The (3 cells whose kytoplasm were buffy stained positively with insulin and there were no pancreatic (3 cells apoptosis.Conclusion1. Clozapine increase slowly serum insulin and the fasting blood glucose and affect glucose tolerance, but no acute influence on blood glucose and serum insulin.2. Clozapine has no effect on pancreatic (3 cell apoptosis in the male C57BL/6 mice.3. Clozapine has no acute effect on the gene expression of GLUT4, but the gene expression of GLUT4 is suppressed by the long term treatment of clozapine. The down-regulation of GLUT4 mRNA probably...