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| Effects of subchronic Olanzapine treatment on metabolism of glycogen and expression of glucose transporter in rats |
| DONG Wenfeng DU Xiangdong |
| Suzhou Psychiatric Hospital, Jiangsu Province, Suzhou 215137, China |
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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.
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[1] Vuk A，Kuzman MR，Baretic M，et al. Diabetic ketoacidosis associated with antipsychotic drugs：case reports and a review of literature [J]. Psychiatr Danub，2017，29（2）：121-135.
[2] Zahan T，Akhter N，Mullick MSI，et al. Metabolic risk factor-profile in patients on treatment with second generation antipsychotics [J]. Bangladesh Med Res Counc Bull，2015， 41（3）：144-150.
[3] 白艳乐，江开达.新型抗精神病药物与高血糖及Ⅱ型糖尿病[J].上海精神医学，2001，13（4）：228-231.
[4] 徐芬娟，沈飞霞.血糖波动的研究进展[J].中国糖尿病杂志，2014，22（9）：852-855.
[5] Al-Zoairy R，Ress C，Tschoner A，et al. The effects of psychotropic drugs on the regulation of glucose metabolism [J]. Curr Diabetes Rev，2013，9（5）：362-370.
[6] Zhang Y，Liu Y，Su Y，et al. The metabolic side effects of 12 antipsychotic drugs used for the treatment of schizophrenia on glucose：a network meta-analysis [J]. BMC Psychiatry，2017，17（1）：373.
[7] Iwaku K，Otuka F，Taniyama M. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine [J]. Intern Med，2017，56（3）：335-339.
[8] Kumar A，Narayanaswamy JC，Venkatasubramanian G，et al. Prevalence of metabolic syndrome and its clinical correlates among patients with bipolar disorder [J]. Asian J Psychiatr，2017，26：109-114.
[9] 李洁，姚贵忠，刘丽娟，等.非典型抗精神病药物相关代谢不良反应的系统评价和meta-分析[J].中国心理卫生杂志，2015，29（3）：210-216.
[10] 徐劲节，Dake Qi，崔东红.奥氮平致代谢紊乱和心血管疾病研究进展[J].中国神经精神疾病杂志，2016，42（5）：303-306.
[11] Fontana L，Eagon JC，Trujillo ME，et al. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans [J]. Diabetes，2007，56（4）：1010-1013.
[12] 李妍，崔文洁，曲伸.非典型糖尿病研究进展[J].第二军医大学学报，2015，36（10）：1112-1116.
[13] Bano G. Glucose homeostasis，obesity and diabetes [J]. Best Pract Res Clin Obestet Gynaecol，2013，27（5）：715-726.
[14] H?覬jlund K. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance [J]. Dan Med J，2014，61（7）：B4890.
[15] Chen FC，Shen KP，Chen JB，et al. PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes [J]. Kaohsiung J Med Sci， 2018，34（1）：14-21.
[16] Maria Z，Campolo AR，Scherlag BJ，et al. Dysregulation of insulin-sensitive glucose transporters during insulin resistance-induced atrial fibrillation [J]. Biochim Biophys Acta Mol Basis Dis，2018，1864（4 Pt A）：987-996.
[17] Wasik AA，Lehtonen S. Glucose transporters in diabetic kidney disease-friends or foes？[J]. Front Endocrinol（Lausanne），2018，9：155.
[18] Tsytkin-Kirschenzweig S，Cohen M，Nahmias Y. Tracking GLUT2 translocation by live-cell imaging [J]. Methods Mol Biol，2018，1713：241-254.
[19] Turnbull J，Tiberia E，Pereira S，et al. Deficiency of a glycogen synthase-associated protein，Epm2aip1，causes decreased glycogen synthesis and hepatic insulin resistance [J]. J Biol Chem，2013，288（48）：34627-34637.
[20] Zhao X，Lu Y，Wang F. High glucose reduces hepatic glycogenesis by suppression of microRNA-152 [J]. Mol Med Rep，2014，10（4）：2073-2078. |
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