Schmitz F J, Rösen P, Reinauer H
Diabetes Research, Department of Clinical Biochemistry, Dusseldorf, Germany.
Horm Metab Res. 1995 Dec;27(12):515-22. doi: 10.1055/s-2007-980016.
The effect of Etomoxir as a carnitine palmitoyl transferase I-inhibitor was investigated in normal and chronic diabetic rats. Etomoxir (18 mg/kg) was given daily for 8 days by intraperitoneal injection in order to inhibit the oxidation of fatty acids and to increase the metabolism of glucose. This carnitine palmitoyl transferase I-inhibitor significantly improved and almost normalized the decreased heart function in chronic diabetic rats. Additionally to the improvement of ventricular heart function, alterations in the conducting system of the diabetic heart were significantly ameliorated. The serum concentrations of glucose, glycerol, cholesterol, tricylglycerol, phospholipids, and beta-hydroxybutyrate were significantly lower in comparison to untreated diabetic animals, while the serum concentration of free fatty acids markedly increased. In addition to the improvement of ventricular heart function, the carnitine content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased in the Etomoxir-treated rats. On the other hand, the lipid content of heart and liver increased significantly. Thus, Etomoxir may be valuable not only as a potential anti-diabetic drug but also as a lipid-lowering agent for the treatment of diabetic related dyslipoproteinaemias and, in addition, as an agent in the treatment of diabetic cardiomyopathy. However, a long-term evaluation of the metabolic consequences of the blocked carnitine palmitoyltransferase I is necessary.
在正常大鼠和慢性糖尿病大鼠中研究了依托莫西作为肉碱棕榈酰转移酶I抑制剂的作用。通过腹腔注射每日给予依托莫西（18mg/kg），持续8天，以抑制脂肪酸氧化并增加葡萄糖代谢。这种肉碱棕榈酰转移酶I抑制剂显著改善了慢性糖尿病大鼠心脏功能下降的情况，几乎使其恢复正常。除了改善心室心脏功能外，糖尿病心脏传导系统的改变也得到了显著改善。与未治疗的糖尿病动物相比，血清葡萄糖、甘油、胆固醇、三酰甘油、磷脂和β-羟基丁酸的浓度显著降低，而血清游离脂肪酸浓度显著升高。除了改善心室心脏功能外，依托莫西治疗的大鼠心脏和肝脏的肉碱含量增加。另一方面，依托莫西治疗的大鼠心脏和肝脏的脂质含量显著增加。因此，依托莫西不仅可能作为一种潜在的抗糖尿病药物有价值，而且作为一种降脂药物用于治疗糖尿病相关的血脂异常，此外，还可作为治疗糖尿病性心肌病的药物。然而，有必要对肉碱棕榈酰转移酶I被阻断后的代谢后果进行长期评估。
