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首页> 外文期刊>Cell metabolism >Antidiabetic effects of IGFBP2, a leptin-regulated gene.
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Antidiabetic effects of IGFBP2, a leptin-regulated gene.

机译：IGFBP2（一种瘦素调节基因）的抗糖尿病作用。

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We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma glucose and insulin concentration. We found that a leptin dose of 12.5 ng/hr significantly lowers blood glucose and that 25 ng/hr of leptin normalizes plasma glucose and insulin without significantly reducing body weight, establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 (IGFBP2) as being regulated by leptin with a similarly high potency. Overexpression of IGFBP2 by an adenovirus reversed diabetes in insulin-resistant ob/ob, Ay/a, and diet-induced obese mice, as well as insulin-deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a 3-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment of ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
机译：我们通过确定瘦素治疗ob / ob小鼠降低血浆葡萄糖和胰岛素浓度的最低剂量，来测试瘦素是否能够独立于体重减轻而改善糖尿病。我们发现，瘦素剂量为12.5 ng / hr会显着降低血糖，而瘦素25 ng / hr可使血浆葡萄糖和胰岛素正常化，而不会显着降低体重，从而证明瘦素对葡萄糖代谢发挥了最有效的作用。为了找到这种作用的可能介体，我们使用微阵列分析了肝mRNA，并鉴定出IGF结合蛋白2（IGFBP2）受瘦素的调节，具有相似的高效力。腺病毒过量表达IGFBP2可逆转胰岛素抵抗的ob / ob，Ay / a和饮食诱导的肥胖小鼠以及胰岛素缺乏的链脲佐菌素治疗的小鼠的糖尿病。高胰岛素钳夹研究显示，IGFBP2治疗ob / ob小鼠后，肝胰岛素敏感性提高了3倍。这些结果表明，IGFBP2可以调节葡萄糖代谢，这一发现对糖尿病的发病机理和治疗具有潜在的意义。

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