Anti-CD44 Antibody Treatment Lowers Hyperglycemia and Improves Insulin Resistance, Adipose Inflammation, and Hepatic Steatosis in Diet-Induced Obese Mice
Anti-CD44 Antibody Treatment Lowers Hyperglycemia and Improves Insulin Resistance, Adipose Inflammation, and Hepatic Steatosis in Diet-Induced Obese Mice
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DOI：
10.2337/db14-0149
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发表时间：
2015-03-01
期刊：
影响因子：
7.7
通讯作者：
Butte, Atul J.
中科院分区：
文献类型：
--
作者：
Kodama, Keiichi;Toda, Kyoko;Butte, Atul J.
2 型糖尿病 (T2D) 是一种代谢性疾病，影响全球超过 3.7 亿人。其特点是肥胖引起的胰岛素抵抗，越来越多的证据表明肥胖和胰岛素抵抗之间的因果关系与内脏脂肪组织炎症有关。然而，使用抗炎药物治疗胰岛素抵抗和 T2D 并不常见。我们最近应用生物信息学方法开放公共数据，发现CD44在脂肪组织炎症和胰岛素抵抗的发展中发挥着关键作用。在本报告中，我们通过在高脂肪饮食小鼠模型中每日注射抗 CD44 单克隆抗体 (mAb) 来研究 CD44 在 T2D 中的作用。与对照组相比，四周的 CD44 mAb 治疗可抑制内脏脂肪组织炎症，并将空腹血糖水平、体重增加、肝脏脂肪变性和胰岛素抵抗降低至与二甲双胍和吡格列酮治疗相当或更好的水平。这些发现表明，CD44 mAb 可能通过打破肥胖与胰岛素抵抗之间的联系，作为治疗 T2D 的原型药物。
Type 2 diabetes (T2D) is a metabolic disease affecting >370 million people worldwide. It is characterized by obesity-induced insulin resistance, and growing evidence has indicated that this causative link between obesity and insulin resistance is associated with visceral adipose tissue inflammation. However, using anti-inflammatory drugs to treat insulin resistance and T2D is not a common practice. We recently applied a bioinformatics methodology to open public data and found that CD44 plays a critical role in the development of adipose tissue inflammation and insulin resistance. In this report, we examined the role of CD44 in T2D by administering daily injections of anti-CD44 monoclonal antibody (mAb) in a high-fat-diet mouse model. Four weeks of therapy with CD44 mAb suppressed visceral adipose tissue inflammation compared with controls and reduced fasting blood glucose levels, weight gain, liver steatosis, and insulin resistance to levels comparable to or better than therapy with the drugs metformin and pioglitazone. These findings suggest that CD44 mAb may be useful as a prototype drug for therapy of T2D by breaking the links between obesity and insulin resistance.