Abstract Objective To study the effects of subchronic Olanzapine treatment on the metabolism of glycogen and expression of glucose transporter in rats and to investigate the possible mechanism of Olanzapine′s effects on glycometabolism. Methods Twelve healthy male SPF grade Sprague-Dawley (SD) rats were divided into control group (n = 6) and drug group (n = 6) according to random number table method. Rats in drug group were given 2.1 mg/kg Olanzapine suspension per day according to body weight by gavage and rats in control group were given the same volume of distilled water by gavage for 63 days. The food intake, change of body weight, levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected periodically. The insulin sensitivity index (ISI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. After 63 days, the liver, muscle and adipose tissues were collected and the content of glycogen and activity of glycogensynthase (GS) in liver and muscle tissues were detected. Western blot was used to assay the protein expression of GS in liver and muscle tissues and glucose transporter (GLUT) in liver, muscle and adipose tissues. PCR was used to assay the mRNA expression of GLUT in liver, muscle and adipose tissues. Results Compared to rats of control group, the subchronic Olanzapine treatment led to an increase of food intake, body weight, FBG and FINS in drug group, while the content of glycogen was reduced, the activity of GS was increased but the protein expression of GS was unchanged; the protein and mRNA expression of GLUT in liver, muscle and adipose tissues were decreased with highly statistically significant differences (P ＜ 0.01). Conclusion Subchronic Olanzapine treatment can increase glycogenolysis, decrease the capacity of glucose transport and result in generating insulin resistance, which may be one of the mechanisms lead to abnormal glucose metabolism after subchronic administration of Olanzapine.
DONG Wenfeng DU Xiangdong. Effects of subchronic Olanzapine treatment on metabolism of glycogen and expression of glucose transporter in rats[J]. 中国医药导报, 2019, 16(3): 11-15.
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