Xiang H, Heyliger C E, McNeill J H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Diabetes. 1988 Nov;37(11):1542-8. doi: 10.2337/diab.37.11.1542.
Numerous experimental studies have implied a link between diabetes-induced abnormal lipid buildup in the myocardium and the development of cardiomyopathy. Because the diabetic state in rats is associated with lowered T3 (triiodothyronine) and T4 levels and because diabetic patients excrete large amounts of myo-inositol, a lipotropic agent, we investigated the effects of myo-inositol and T3 on the elevated myocardial lipid levels and depressed cardiac performance of streptozocin (55 mg/kg i.v.)-induced diabetic (STZ-D) rats. myo-inositol (2.5 g.kg-1.day-1 in the drinking water) and T3 (30 micrograms.kg-1.day-1 s.c.) were given for an 8-wk period 3 days after diabetes induction. Untreated diabetic rats were characterized by a decreased rate of body weight gain, hyperglycemia, and hypoinsulinemia, which were not altered after myo-inositol and/or T3 treatment. Thyroid status of diabetic animals was normalized by T3 alone or in combination with myo-inositol but not by myo-inositol alone. The elevations in plasma and myocardial lipids associated with the diabetic state were prevented by myo-inositol treatment. However, the plasma lipid and myocardial cholesterol levels in diabetic rats remained elevated or were further increased with treatment with T3 or myo-inositol plus T3. myo-inositol treatment partially improved cardiac performance in STZ-D rats. T3 treatment alone did not prevent cardiac dysfunction in diabetic rats. There was, however, some improvement in heart function in the groups treated with both myo-inositol and T3, coinciding with a significant decrease in the myocardial triacylglycerol level. The data indicate that a possible correlation may exist between elevated myocardial triacylglycerol levels and cardiac dysfunction in diabetic rats.
众多实验研究表明,糖尿病诱导的心肌脂质异常蓄积与心肌病的发生之间存在关联。由于大鼠的糖尿病状态与三碘甲状腺原氨酸(T3)和甲状腺素(T4)水平降低有关,且糖尿病患者会排泄大量的促脂物质肌醇,因此我们研究了肌醇和T3对链脲佐菌素(55 mg/kg静脉注射)诱导的糖尿病(STZ-D)大鼠心肌脂质水平升高和心脏功能降低的影响。在诱导糖尿病3天后,给予肌醇(饮用水中2.5 g·kg⁻¹·天⁻¹)和T3(30 μg·kg⁻¹·天⁻¹皮下注射),持续8周。未经治疗的糖尿病大鼠表现为体重增加率降低、高血糖和低胰岛素血症,在给予肌醇和/或T3治疗后这些情况并未改变。单独使用T3或与肌醇联合使用可使糖尿病动物的甲状腺状态恢复正常,但单独使用肌醇则不能。肌醇治疗可预防与糖尿病状态相关的血浆和心肌脂质升高。然而,糖尿病大鼠的血浆脂质和心肌胆固醇水平在给予T3或肌醇加T3治疗后仍保持升高或进一步升高。肌醇治疗可部分改善STZ-D大鼠的心脏功能。单独使用T3治疗不能预防糖尿病大鼠的心脏功能障碍。然而,同时给予肌醇和T3治疗的组心脏功能有一定改善,同时心肌三酰甘油水平显著降低。数据表明,糖尿病大鼠心肌三酰甘油水平升高与心脏功能障碍之间可能存在相关性。