Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet
Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet
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DOI：
10.1042/cs20070122
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发表时间：
2008-01-01
期刊：
影响因子：
6
通讯作者：
Welsh, Nils
中科院分区：
文献类型：
--
作者：
Hagerkvist, Robert;Jansson, Leif;Welsh, Nils
本研究的目的是调查伊马替尼是否影响HF（高脂）喂养大鼠的胰岛素敏感性和葡萄糖处置。Sprague-Dawley大鼠喂食标准颗粒状大鼠饲料（低脂饮食）或HF饮食（60%脂肪）8周。在HF饮食方案的最后10天期间，大鼠每天通过管饲法接受单独的盐水或伊马替尼（50或100 mg/kg体重）。较高剂量的伊马替尼导致HF治疗大鼠的腰肌脂肪垫重量降低。在正常血高胰岛素钳夹条件下，HF喂养的大鼠表现出胰岛素浓度增加和葡萄糖处置减少。较低剂量（50 mg/kg体重），但不是较高剂量（100 mg/kg体重），伊马替尼使低脂肪喂养大鼠的胰岛素敏感性和葡萄糖处置正常化，而不影响葡萄糖代谢。空腹和高胰岛素血症条件下的肝脏葡萄糖生成仅受到伊马替尼的微弱影响。我们的结论是，中等剂量的伊马替尼有效地抵消HF诱导的外周胰岛素抵抗，并通过伊马替尼增加肌肉和脂肪组织中的胰岛素作用的机制的进一步研究可能会产生治疗2型糖尿病的新策略。
The aim of the present study was to investigate whether imatinib affects insulin sensitivity and glucose disposal in HF (high-fat)-fed rats. Sprague-Dawley rats were fed either a standard pelleted rat food (low-fat diet) or an HF diet (60% fat) for 8 weeks. During the last 10 days of the HF diet regime, rats received saline alone or imatinib (50 or 100 mg/kg of body weight) daily by gavage. The higher dose of imatinib resulted in a decreased psoas fat pad weight in the HF-treated rats. Under euglycaemic hyperinsulinaemic clamp conditions, HF-fed rats exhibited increased insulin concentrations and decreased glucose disposal. The lower (50 mg/kg of body weight), but not the higher (100 mg/kg of body weight), dose of imatinib normalized insulin sensitivity and glucose disposal without affecting glucose metabolism in low-fat-fed rats. Hepatic glucose production at both fasting and hyperinsulinaemic conditions was only weakly affected by imatinib. We conclude that a moderate dose of imatinib efficiently counteracts HF-induced peripheral insulin resistance, and that further studies on the mechanisms by which imatinib increases insulin action in muscle and fat tissues might generate novel strategies for the treatment of Type 2 diabetes.