Lucas D, Farez C, Bardou L G, Vaisse J, Attali J R, Valensi P
Laboratoires de Biochimie-Nutrition, Faculté de Médecine de Brest, France.
Fundam Clin Pharmacol. 1998;12(5):553-8. doi: 10.1111/j.1472-8206.1998.tb00985.x.
Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m2). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 mumol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NIDDs, n = 15) when compared to controls (n = 42) (0.21 +/- 0.03, 0.33 +/- 0.03 and 0.30 +/- 0.02, respectively, mean +/- SEM). However, this activity was lower in IDDs when compared to NIDDs (P < 0.05). In obese patients, with (n = 13) or without (n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol (r = 0.42, P < 0.0001), triglycerides (r = 0.44, P < 0.0001) and BMI (r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.
细胞色素P450 2E1（CYP2E1）是一种I相解毒酶，可由长期饮酒诱导产生。它参与多种致癌物的激活以及自由基的生成。由于此前已证实在糖尿病大鼠和肥胖大鼠中该酶会被诱导产生，本研究旨在调查其在血糖控制不佳的糖尿病患者和肥胖患者（体重指数>30kg/m²）中的诱导水平。通过体内氯唑沙宗羟基化试验测定了35例糖尿病患者和17例肥胖患者的CYP2E1活性。尽管糖代谢参数严重紊乱（平均空腹血糖>7.9mmol/L，餐后血糖>12.2mmol/L，果糖胺>326μmol/L），但与对照组（n = 42）相比，胰岛素依赖型糖尿病患者（IDDs，n = 7）和非肥胖非胰岛素依赖型糖尿病患者（NIDDs，n = 15）的CYP2E1活性均未增强（分别为0.21±0.03、0.33±0.03和0.30±0.02，均值±标准误）。然而，与NIDDs相比，IDDs患者的该活性较低（P<0.05）。在肥胖患者中，无论是否患有NIDD（分别为n = 13和n = 17），与对照组相比，CYP2E1活性平均增加了40%。此外，在所有受试者（对照组或患者，n = 74）中发现CYP2E1活性与血清胆固醇（r = 0.42，P<0.0001）、甘油三酯（r = 0.44，P<0.0001）和体重指数（r = 0.36，P<0.001）之间呈正相关。因此，血清胆固醇和/或甘油三酯水平分别高于6.4和1.8mmol/L的受试者，其CYP2E1活性相较于上述水平范围内的受试者平均增加了40%。据信，CYP2E1活性增加的个体更容易受到CYP2E1介导的毒素和致癌物激活所产生的不良影响。
