Evaluation of hepatic CYP2D1 activity and hepatic clearance in type I and type II diabetic rat models, before and after treatment with insulin and metformin

Frequency of Important CYP450 Enzyme Gene Polymorphisms in the Iranian Population in Comparison with Other Major Populations: A Comprehensive Review of the Human Data

“…Modulation of CYP enzymes activity results in altered pharmacokinetics of drugs metabolized by these enzymes [ 6 , 7 ]. Apart from intra-individual changes in the activity of these enzymes by a number of physiological, pathological, and environmental factors [ 8 , 9 , 10 , 11 , 12 ], the expression of CYP genes can present consequential inter-individual variations in the basal expression, giving rise to diversities in the rates of drug elimination and response [ 13 ].…”

Can combination therapy with insulin and metformin improve metabolic function of the liver, in type I diabetic patients? An animal model study on CYP2D1 activity

“…The average metabolic rate of dextromethorphan and hepatic clearance changed from 0.012 ± 0.004 and 6.3 ± 0.1 ml/min in the control group to 0.006 ± 0.001 and 5.2 ± 0.2 ml/min in the untreated type-1 diabetic group, and 0.008 ± 0.003 and 5 ± 0.6 ml/min in the untreated type-2 diabetic rats [1]. In the present study, metabolic rate and hepatic clearance changed to 0.0112 ± 0.0008 and 6.2 ± 0.1 ml/min in the type-1 diabetic group treated with insulin plus metformin, and 0.0149 ± 0.0012 and 6.03 ± 0.06 ml/min in the insulin-receiving type-2 diabetic rats.…”

“…After three weeks of diabetes induction, the IPRL model was used to evaluate the hepatic CYP2D1 activity and hepatic clearance in designed animal groups. The results of the following groups were considered from the previous study [1] in our lab:…”

“…The expression and the activity of cytochrome P450s (CYP450) could be altered by many environmental factors, including medications, gender, smoking, and so on. One of the most important factors receiving special consideration is pathological conditions, such as diabetes, cancer, and hypertension [1][2][3]. On the other hand, the key role of inflammatory and oxidative stress processes in developing the secondary problems caused by diabetes has been shown in many studies [4][5][6].…”

“…Our previous studies confirmed a reduction in rat CYP2D1 activity following type-1 and type-2 diabetes in animal models. Although metformin administration could balance enzyme activity in type-2 diabetes [2], And its effects in patients with type 2 diabetes are being studied [15], insulin therapy in type-1 diabetic rats could not modulate the enzyme activity to the observed levels in healthy control rats despite the good glycemic control [1].…”