Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine
Antidiabetic-drug combination treatment for glucose intolerance in adult female rats treated acutely with olanzapine
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DOI：
10.1016/j.pnpbp.2013.10.006
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发表时间：
2014-01-03
影响因子：
5.6
通讯作者：
Barr, Alasdair M.
中科院分区：
文献类型：
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作者：
Boyda, Heidi N.;Procyshyn, Ric M.;Barr, Alasdair M.
第二代抗精神病药物是治疗精神病的常规药物。其中许多化合物，包括奥氮平，会引起代谢副作用，如糖耐量受损和胰岛素抵抗。单独的抗糖尿病药物可以帮助控制接受抗精神病药物治疗的患者的血糖水平升高，但联合使用抗糖尿病药物的效果从未被研究过，这种药物通常发生在2型糖尿病患者身上。目前，我们比较了三种不同的降糖药二甲双胍(500 mg/kg，P.O.)和罗格列酮(30 mg/kg，P.O.)的疗效。格列本脲(10 mg/kg，P.O.)奥氮平急性给药对成年雌性大鼠代谢紊乱的影响。此外，将这些抗糖尿病药物的双重组合与彼此以及单独的药物进行了面对面的比较。这些动物每天接受两次抗糖尿病药物治疗，然后接受奥氮平(10 mg/kg，ip)的急性治疗。测定空腹血糖和胰岛素水平，然后进行2小时糖耐量试验。与赋形剂治疗的大鼠相比，奥氮平引起了很大且非常显著的葡萄糖耐量异常。罗格列酮降低血糖水平并不显著，而与仅接受奥氮平治疗的动物相比，二甲双胍和格列本脲均显著降低血糖水平。对于抗糖尿病双药联合用药，罗格列酮-二甲双胍组的血糖水平比所有单一抗糖尿病药物都意外增加。然而，在奥氮平治疗后，二甲双胍-格列本脲组和罗格列酮-格列本脲组的血糖水平的下降幅度都明显大于二甲双胍或罗格列酮的单一药物治疗，使血糖水平下降到与仅使用载药剂治疗的动物相当的水平。这些发现表明，在接受抗精神病药物治疗的患者中进一步研究抗糖尿病双药联合治疗是必要的。(C)2013 Elsevier Inc.保留所有权利。
Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500 mg/kg, p.o.), rosiglitazone (30 mg/kg, p.o.) and glyburide (10 mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10 mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2 h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted. (C) 2013 Elsevier Inc. All rights reserved.