Ikeda H, Taketomi S, Sugiyama Y, Shimura Y, Sohda T, Meguro K, Fujita T
Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Arzneimittelforschung. 1990 Feb;40(2 Pt 1):156-62.
The antidiabetic effects of pioglitazone (5-[4-[2-(5-ethyl-2-pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) were examined in normal, obese, and/or diabetic animals. When orally administered to genetically obese and diabetic yellow KK mice (2.4-24.5 mg/kg/d), and Zucker fatty rats (0.1-10 mg/kg/d) for 4 days, pioglitazone markedly decreased hyperglycemia, hyperlipidemia, hyperinsulinemia, and glucose intolerance characterized as insulin resistant states in these animals. Pioglitazone potentiated insulin-mediated glucose metabolism in the diaphragm and adipose tissues of yellow KK mice and enhanced the glycemic response to exogenous insulin in Zucker fatty rats. Four-day administration of pioglitazone (1 mg/kg/d) to aged and obese beagle dogs with moderate insulin resistance decreased plasma glucose and lipids in the fasting state, and postprandial rises in plasma triglyceride. Pioglitazone decreased plasma lipids but did not alter the plasma glucose level in young normal rats. Pioglitazone did not alter plasma glucose and lipid levels in streptozocin-diabetic rats. These results indicate that pioglitazone is effective on abnormal glucose and lipid metabolism associated with insulin resistance by enhancing insulin action on peripheral tissues. Therefore, pioglitazone is expected to be useful in treating obese non-insulin-dependent diabetes.
在正常、肥胖和/或糖尿病动物中研究了吡格列酮（5-[4-[2-(5-乙基-2-吡啶基)乙氧基]苄基]-2,4-噻唑烷二酮，AD-4833，也称为U-72,107E）的抗糖尿病作用。当以口服方式给予遗传性肥胖和糖尿病的黄色KK小鼠（2.4 - 24.5毫克/千克/天）和Zucker肥胖大鼠（0.1 - 10毫克/千克/天）4天时，吡格列酮显著降低了这些动物以胰岛素抵抗状态为特征的高血糖、高血脂、高胰岛素血症和葡萄糖不耐受。吡格列酮增强了黄色KK小鼠膈肌和脂肪组织中胰岛素介导的葡萄糖代谢，并增强了Zucker肥胖大鼠对外源性胰岛素的血糖反应。对具有中度胰岛素抵抗的老年肥胖比格犬给予吡格列酮（1毫克/千克/天）4天，可降低空腹状态下的血浆葡萄糖和脂质，以及餐后血浆甘油三酯的升高。吡格列酮可降低年轻正常大鼠的血浆脂质，但不改变其血浆葡萄糖水平。吡格列酮对链脲佐菌素诱导的糖尿病大鼠的血浆葡萄糖和脂质水平没有影响。这些结果表明，吡格列酮通过增强胰岛素对周围组织的作用，对与胰岛素抵抗相关的异常葡萄糖和脂质代谢有效。因此，吡格列酮有望用于治疗肥胖的非胰岛素依赖型糖尿病。
