Lee M K, Miles P D, Khoursheed M, Gao K M, Moossa A R, Olefsky J M
Department of Medicine, School of Medicine, University of California, San Diego.
Diabetes. 1994 Dec;43(12):1435-9. doi: 10.2337/diab.43.12.1435.
Troglitazone is a new orally active hypoglycemic agent that has been shown to reduce insulin resistance and hyperinsulinemia in both diabetic animal models and non-insulin-dependent diabetes mellitus (NIDDM) subjects. To determine whether this drug could prevent the development of fructose-induced insulin resistance and related abnormalities, we studied the effects of troglitazone on the insulin resistance induced by fructose feeding in rats. Normal male Sprague-Dawley rats were fed a high-fructose diet for 3 weeks with and without troglitazone as a food admixture (0.2%) or were fed normal chow to serve as a control group. In vivo insulin resistnace was measured by the euglycemic hyperinsulinemic clamp technique at two different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol.kg-1.min-1. Fructose feeding markedly reduced submaximal glucose disposal rate (GDR) (113.8 +/- 8.3 vs. 176.0 +/- 5.6 mumol.kg-1.min-1, P < 0.05) and maximal GDR (255.9 +/- 5.6 vs. 313.6 +/- 10.5 mumol.kg-1.min-1, P < 0.05), reduced the suppressibility of submaximal hepatic glucose production (HGP; 45.5 +/- 5.0 vs. 11.7 +/- 5.0 mumol.kg-1.min-1, P < 0.05), and resulted in hypertriglyceridemia and hypertension. Troglitazone treatment completely restored the GDR (submaximal 158.2 +/- 5.6, maximal 305.3 +/- 6.1 mumol.kg-1.min-1) and submaximal HGP (9.4 +/- 2.8 mumol.kg-1.min-1) to control levels and also normalized the elevated plasma triglyceride concentration and systolic blood pressure levels in fructose-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
曲格列酮是一种新型口服活性降糖药，在糖尿病动物模型和非胰岛素依赖型糖尿病（NIDDM）患者中均已显示出可降低胰岛素抵抗和高胰岛素血症。为了确定该药物是否能预防果糖诱导的胰岛素抵抗及相关异常的发生，我们研究了曲格列酮对果糖喂养大鼠诱导的胰岛素抵抗的影响。正常雄性斯普拉-道利大鼠被给予高果糖饮食3周，其中一组饮食中添加曲格列酮（0.2%）作为食物添加剂，另一组不添加，还有一组喂食正常食物作为对照组。通过正常血糖高胰岛素钳夹技术，在两种不同的胰岛素输注速率下，即29（次最大刺激）和290（最大刺激）pmol·kg-1·min-1，测量体内胰岛素抵抗。果糖喂养显著降低了次最大葡萄糖处置率（GDR）（113.8±8.3对176.0±5.6μmol·kg-1·min-1，P<0.05）和最大GDR（255.9±5.6对313.6±10.5μmol·kg-1·min-1，P<0.05），降低了次最大肝脏葡萄糖生成（HGP）的抑制率（45.5±5.0对11.7±5.0μmol·kg-1·min-1，P<0.05），并导致高甘油三酯血症和高血压。曲格列酮治疗可使GDR（次最大时为158.2±5.6，最大时为305.3±6.1μmol·kg-1·min-1）和次最大HGP（9.4±2.8μmol·kg-1·min-1）完全恢复至对照水平，还使果糖喂养大鼠升高的血浆甘油三酯浓度和收缩压水平恢复正常。（摘要截断于250字）
