The mechanisms underlying olanzapine-induced insulin resistance via the brown adipose tissue and the therapy in rats.
The mechanisms underlying olanzapine-induced insulin resistance via the brown adipose tissue and the therapy in rats.
复制标题
奥氮平通过棕色脂肪组织诱导胰岛素抵抗的机制及治疗
DOI：
10.1080/21623945.2022.2026590
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发表时间：
2022-12
期刊：
影响因子：
3.3
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wang J;Wu Q;Zhou Y;Yu L;Yu L;Deng Y;Tu C;Li W
长期使用奥氮平治疗可导致胰岛素抵抗（IR）的发生率迅速上升，目前尚无更好的预防方法。我们的研究旨在揭示奥氮平诱导胰岛素抵抗的机制，并寻找合适的药物干预措施。本研究首先采用奥氮平灌胃2个月建立大鼠胰岛素抵抗模型，并采用葛根芩连汤主活性成分合剂进行治疗。采用PET/CT扫描检测棕色脂肪组织（BAT）活性，Western blot和实时荧光定量PCR检测GLUT4和UCP1的表达。结果表明，长期给药奥氮平可使大鼠糖耐量下降，产生胰岛素抵抗，葛根芩连汤可改善这一副作用。PET/CT扫描结果显示，胰岛素抵抗大鼠的BAT活性明显低于葛根芩连汤治疗大鼠。胰岛素抵抗组GLUT4和UCP1的表达明显降低，葛根芩连汤治疗可能上调了GLUT4和UCP1的表达。体内、体外实验结果一致。我们证明了奥氮平可以通过降低UCP1的表达诱导体外和体内IR；因此，抑制BAT的产热作用并损害葡萄糖摄取。更重要的是，我们展示了一种可能的新策略来改善葛根芩连汤对奥氮平诱导的IR。
ABSTRACT A rapid increase has been observed in insulin resistance (IR) incidence induced by a long-term olanzapine treatment with no better ways to avoid it. Our study aimed to demonstrate the mechanism underlying the olanzapine-induced insulin resistance and find appropriate drug interventions. In this study, firstly, we constructed rat insulin resistance model using a two-month gavage of olanzapine and used the main active ingredient mixture of Gegen Qinlian Decoction for the treatment. The activity of brown adipose tissue (BAT) was measured using the PET/CT scan, whereas Western blot and quantitative real-time PCR were used to detect the expression of GLUT4 and UCP1. The results showed that the long-term administration of olanzapine impaired glucose tolerance and produced insulin resistance in rats, while Gegen Qinlian Decoction could improve this side effect. The results of the PET/CT scan showed that the BAT activity in the insulin-resistant rats was significantly lower than that of the Gegen Qinlian Decoction treated rats. Also, the expression of GLUT4 and UCP1 in the insulin resistance group showed a significant decrease, which could be up-regulated by Gegen Qinliane Decoction treatment. The results of both in vivo and in vitro experiments were consistent. we demonstrated that the olanzapine could induce IR in vitro and in vivo by decreasing the expression of UCP1; thus, suppressing the thermogenesis of BAT and impairing glucose uptake. More importantly, we demonstrated a possible novel strategy to improve the olanzapine-induced IR by Gegen Qinlian Decoction.
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DOI：
10.3390/ph14030238
发表时间：
2021-03-08
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Carli M;Kolachalam S;Longoni B;Pintaudi A;Baldini M;Aringhieri S;Fasciani I;Annibale P;Maggio R;Scarselli M
通讯作者：
Scarselli M
影响因子：
3.7
作者：
Knudsen, Jenny Dahl;Andersen, Stig Ejdrup
通讯作者：
Andersen, Stig Ejdrup
影响因子：
8.2
作者：
Li, De-juan;Yue, Qin;Hu, Chang-hua
通讯作者：
Hu, Chang-hua
DOI：
10.1016/j.biocel.2012.09.023
发表时间：
2013-01-01
影响因子：
4
作者：
Clarke, Kieran J.;Porter, Richard K.
通讯作者：
Porter, Richard K.
影响因子：
2.9
作者：
Liu, Xuemei;Feng, Xiyu;Hu, Chang-Hua
通讯作者：
Hu, Chang-Hua