大鼠中四氧嘧啶和链脲佐菌素诱导的糖尿病比较：对微粒体药物代谢的不同影响。

Comparison of alloxan and streptozotocin induced diabetes in rats: differential effects on microsomal drug metabolism.

Vega P, Gaule C, Mancilla J, Del Villar E

Department of Biochemistry, Faculty of Medicine, University of Chile, Santiago.

Gen Pharmacol. 1993 Mar;24(2):489-95. doi: 10.1016/0306-3623(93)90336-v.

Abstract

Liver microsomes from alloxan or streptozotocin diabetic rats displayed differential drug metabolizing abilities in vitro. 2. Only streptozotocin liver microsomes exhibited changes in the cytochrome P-450 normal spectral characteristics. 3. Overall testosterone metabolism was significantly increased in streptozotocin diabetic liver microsomes, whereas it was markedly decreased in alloxan diabetes. Mixed function oxidase activity for aminopyrine was similar. 4. Glucuronidation reaction rates towards morphine, oestrone and p-nitrophenol were also markedly distinct in both models as well as after insulin treatment. 5. Results suggest that diabetogenic agents modify sex related isoenzymes of cytochrome P-450 differently and selectively reduce the synthesis of certain UDP-glucuronyltransferase forms.

摘要

来自四氧嘧啶或链脲佐菌素诱导的糖尿病大鼠的肝微粒体在体外表现出不同的药物代谢能力。2. 只有链脲佐菌素诱导的肝微粒体细胞色素P-450的正常光谱特征出现了变化。3. 链脲佐菌素诱导的糖尿病肝微粒体中睾酮的整体代谢显著增加，而在四氧嘧啶糖尿病中则明显降低。氨基比林的混合功能氧化酶活性相似。4. 两种模型以及胰岛素治疗后，吗啡、雌酮和对硝基苯酚的葡萄糖醛酸化反应速率也明显不同。5. 结果表明，致糖尿病药物对细胞色素P-450的性别相关同工酶有不同的修饰作用，并选择性地减少某些尿苷二磷酸葡萄糖醛酸基转移酶形式的合成。