Introduction Conversion in the metabolism of drugs occurs in diabetes mellitus. Considering the importance of metabolic enzymes’ activities on the efficacy and safety of medicines, the changes in liver enzymatic activity of CYP2D1 and its related hepatic clearance, by using Dextromethorphan as probe in the animal model of type I and type II diabetes, before and after treatment, was assessed in this study. Methods Male Wistar rats were randomly divided into 6 groups. Seven days after induction of diabetes type I and type II, treatment groups were received insulin and metformin daily for 14 days, respectively. In day 21, rats were subjected to liver perfusion by Krebs-Henseleit buffer containing Dextromethorphan as CYP2D1 probe. Perfusate samples were analyzed by HPLC fluorescence method in order to evaluate any changes in CYP2D1 activity. Results The average metabolic ratio of dextromethorphan and hepatic clearance were changed from 0.012 ± 0.004 and 6.3 ± 0.1 in the control group to 0.006 ± 0.0008 and 5.2 ± 0.2 in the untreated type I diabetic group, and 0.008 ± 0.003 and 5.0 ± 0.6 in the untreated type II diabetic rats. Finally, the mean metabolic ratio and hepatic clearance were changed to 0.008 ± 0.001 and 5.4 ± 0.1, and 0.013 ± 0.003 and 6.1 ± 0.4 in the treated groups with insulin and metformin, respectively. Conclusion In type I diabetic rats, corresponding treatment could slightly improve enzyme activity, whereas the hepatic clearance and enzyme activity reached to the normal level in type II group. Graphical abstract .

中文翻译：

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胰岛素和二甲双胍治疗前后 I 型和 II 型糖尿病大鼠模型肝脏 CYP2D1 活性和肝脏清除率的评估

介绍 药物代谢的转化发生在糖尿病中。考虑到代谢酶活性对药物疗效和安全性的重要性，CYP2D1的肝酶活性变化及其相关的肝脏清除率，以右美沙芬为探针在I型和II型糖尿病动物模型中，前后治疗，在本研究中进行了评估。方法雄性Wistar大鼠随机分为6组。诱导 I 型和 II 型糖尿病 7 天后，治疗组分别每天接受胰岛素和二甲双胍治疗 14 天。在第 21 天，用含有右美沙芬作为 CYP2D1 探针的 Krebs-Henseleit 缓冲液对大鼠进行肝脏灌注。通过 HPLC 荧光方法分析灌注液样品以评估 CYP2D1 活性的任何变化。结果右美沙芬与肝脏清除率的平均代谢比从对照组的0.012±0.004和6.3±0.1变为未治疗的I型糖尿病组的0.006±0.0008和5.2±0.2，以及±0.008±0.003和0.5未经治疗的 II 型糖尿病大鼠。最后，胰岛素和二甲双胍治疗组的平均代谢率和肝脏清除率分别变为 0.008±0.001 和 5.4±0.1，以及 0.013±0.003 和 6.1±0.4。结论 I型糖尿病大鼠经相应治疗后酶活性略有提高，而II型组肝清除率和酶活性均达到正常水平。图形概要 。在未治疗的 I 型糖尿病组中为 0008 和 5.2 ± 0.2，在未治疗的 II 型糖尿病大鼠中为 0.008 ± 0.003 和 5.0 ± 0.6。最后，胰岛素和二甲双胍治疗组的平均代谢率和肝脏清除率分别变为 0.008±0.001 和 5.4±0.1，以及 0.013±0.003 和 6.1±0.4。结论 I型糖尿病大鼠经相应治疗后酶活性略有提高，而II型组肝清除率和酶活性均达到正常水平。图形概要 。在未治疗的 I 型糖尿病组中为 0008 和 5.2 ± 0.2，在未治疗的 II 型糖尿病大鼠中为 0.008 ± 0.003 和 5.0 ± 0.6。最后，胰岛素和二甲双胍治疗组的平均代谢率和肝脏清除率分别变为 0.008±0.001 和 5.4±0.1，以及 0.013±0.003 和 6.1±0.4。结论 I型糖尿病大鼠经相应治疗后酶活性略有提高，而II型组肝清除率和酶活性均达到正常水平。图形概要 。分别。结论 I型糖尿病大鼠经相应治疗后酶活性略有提高，而II型组肝清除率和酶活性均达到正常水平。图形概要 。分别。结论 I型糖尿病大鼠经相应治疗后酶活性略有提高，而II型组肝清除率和酶活性均达到正常水平。图形概要 。