Metformin improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats
Metformin improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats
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DOI：
10.1046/j.1463-1326.2002.00178.x
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发表时间：
2002-01-01
影响因子：
5.8
通讯作者：
Anuradha, CV
中科院分区：
文献类型：
--
作者：
Anurag, P;Anuradha, CV
目的：给正常大鼠喂食富含果糖的食物可引起胰岛素抵抗、高胰岛素血症和糖代谢紊乱。二甲双胍是一种抗糖尿病药物，可提高2型糖尿病患者的胰岛素敏感性。先前的研究表明，二甲双胍可以改善果糖喂养大鼠的胰岛素敏感性。本研究的目的是确定二甲双胍治疗对喂食富含果糖饮食的大鼠的总体脂质代谢和脂质过氧化的影响，从而导致胰岛素抵抗。高胰岛素血症和高血糖与过氧化脂质水平的关系也进行了研究。材料与方法：实验动物分为两批。一组饲喂标准日粮，另一组饲喂富含果糖的日粮（72 g/100 g饲料）。2周后，每批大鼠再分为两组。一组给予二甲双胍（50 mg/kg /天，水中），另一组给予标准饮食并作为对照。结果：高果糖喂养导致高胰岛素血症、高血糖、血脂及脂质代谢改变。血浆和组织脂质过氧化物明显升高。二甲双胍（50mg /kg/天）与血浆胰岛素水平和血脂改变的显著正常化相关。这些大鼠血浆中的脂蛋白脂肪酶（LPL）和卵磷脂胆固醇酰基转移酶（LCAT）活性也明显高于未处理的果糖喂养大鼠。血浆和组织中脂质过氧化物含量降低，血浆胰岛素和血糖水平与血浆脂质过氧化物呈显著正相关。结论：我们得出结论，在果糖喂养的大鼠中，除了脂质代谢紊乱外，脂质过氧化也会增强。血浆胰岛素水平可能导致了过氧化作用的增加。二甲双胍治疗大鼠胰岛素作用的改善可能是果糖喂养引起的这些异常改善的原因。
Aim: Insulin resistance, hyperinsulinaemia and disturbances in glucose metabolism can be produced in normal rats by feeding them a fructose-enriched diet. Metformin, an antidiabetic drug, enhances insulin sensitivity in type 2 diabetic patients. Previous studies have shown that metformin improves insulin sensitivity in fructose-fed rats. The aim of this study was to determine the effect of metformin treatment on overall lipid metabolism and lipid peroxidation in rats that were fed a fructose-enriched diet, which leads to insulin resistance. The relationship between hyperinsulinaemia and hyperglycaemia with lipid peroxide levels was also investigated.Materials and Methods: The animals were divided into two batches. One batch received a standard diet and the other was fed a fructose-enriched diet (72 g/100 g feed). After 2 weeks, each batch of rats was subdivided into two groups. One group received metformin (50 mg/kg per day in water) and the other received the standard diet and served as control.Results: High fructose feeding resulted in hyperinsulinaemia, hvperglycaemia and alterations in lipids and lipid metabolism. and plasma and tissue lipid peroxides were significantly elevated. Administration of metformin (50 mg/kg/day) was associated with significant normalization of plasma insulin level and lipid alterations. These rats also showed significantly higher lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) activities in plasma than untreated, fructose-fed rats. Lipid peroxides content was also decreased in plasma and tissues, Significant positive correlations were observed between the levels of plasma insulin and plasma glucose with plasma lipid peroxides.Conclusions: We conclude that enhanced lipid peroxidation occurs in addition to disturbances in lipid metabolism in fructose-fed rats. Plasma insulin level probably contributes to this increased peroxidation. Improved insulin action in metformin-treated rats could be responsible for the amelioration of these abnormalities induced by fructose feeding.