Ai-Luen Wu Fibroblast Growth Factor Receptor 1 Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of

Ai-Luen Wu Fibroblast Growth Factor Receptor 1 Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of

year, opt for the sugar-free egg nog. diseases in the near future. Unfortunately, a miracle drug won't be available in time for the holidays, so perhaps, this receptor-targeting mechanism, these R1MAbs could enter human clinical trials for diabetes and other obesity-related homodimerization in brown adipose tissue. With improved pharmacokinetics over FGF21, in addition to a specific also shed light on the mechanism of action of their R1MAbs, showing that they work via FGFR et al. Wu and obesity. the diabetic mice to lose weight, indicating that this antibody agonist of FGFR1 is a dual-action drug for both diabetes 1 month without reaching dangerously low blood glucose concentrations (hypoglycemia). The R1MAbs also helped R1MAb-treated mice were normalized and remained at lower levels compared to placebo-treated mice for more than were injected once with either R1MAbs or a control antibody. Within 1 week, blood glucose concentrations in the present in the pancreas and in brown and white adipose tissues. Diabetic mice with high blood sugar (hyperglycemia) a receptor −− binds several forms of the FGFR throughout the body, the phage-derived R1MAbs bound only to FGFR1 which targeted tissues that play key roles in diabetes and obesity, including adipose (fat) tissue. In contrast to FGF21, . identified monoclonal antibodies (R1MAbs) that were specifically et al effects. Using phage display technology, Wu The authors reasoned that robust drugs that closely mimic FGF21 function would similarly exert antidiabetic disease in mice. colleagues describe an antibody-based FGF21 mimic that circumvents these limitations to overcome metabolic pharmacokinetics as well as concerns over negative effects of modified FGF21 proteins. In this issue, Wu and treadmill. However, attempts to use this fat-burning factor in humans have not been successful, owing to poor diabetic mice treated with FGF21 regain normal metabolism and lose weight, even without spending hours on a and their receptors (FGFRs), with some factors showing disease-reversing capabilities. For instance, overweight, the molecular level, obesity and type 2 diabetes can be linked by the fibroblast growth factor (FGF) family of proteins It's fun to indulge in holiday cheer, if only a holiday miracle allowed one to avoid the often-linked weight gain. At Getting at Brown Fat

在节日里纵情欢乐是很开心的事，要是有个节日奇迹能让人避免常常伴随而来的体重增加就好了。从分子层面来说，肥胖和2型糖尿病可以通过成纤维细胞生长因子（FGF）蛋白家族及其受体（FGFR）联系起来，一些因子显示出逆转疾病的能力。例如，接受FGF21治疗的糖尿病小鼠即使没有在跑步机上花费数小时，也能恢复正常代谢并减轻体重。然而，由于药代动力学不佳以及对修饰的FGF21蛋白负面影响的担忧，在人类中使用这种燃脂因子的尝试并不成功。在本期中，吴等人描述了一种基于抗体的FGF21模拟物，它规避了这些限制，以克服代谢疾病。作者推断，与FGF21功能紧密相似的强效药物将同样发挥抗糖尿病作用。 吴等人利用噬菌体展示技术，鉴定出了特异性的单克隆抗体（R1MAbs），这些抗体具有多种效果。与FGF21不同，噬菌体衍生的R1MAbs仅与在糖尿病和肥胖中起关键作用的组织（包括脂肪组织）中的FGFR1结合，而FGF21在全身与几种形式的FGFR结合。患有高血糖（高血糖症）的糖尿病小鼠在胰腺以及棕色和白色脂肪组织中存在FGFR1。给小鼠注射一次R1MAbs或对照抗体，在1周内，接受R1MAbs治疗的小鼠血糖浓度恢复正常，并且与接受安慰剂治疗的小鼠相比，在超过1个月的时间里保持在较低水平，且没有达到危险的低血糖浓度。R1MAbs还帮助糖尿病小鼠减轻体重，这表明这种FGFR1抗体激动剂是一种对糖尿病和肥胖都有双重作用的药物。 这些R1MAbs可能会进入针对糖尿病和其他与肥胖相关疾病的人体临床试验。在棕色脂肪组织中，除了具有特异性外，与FGF21相比，它们还具有改善的药代动力学，并且还阐明了其R1MAbs的作用机制，表明它们通过FGFR等起作用。不幸的是，在假期来临之前不会有神奇的药物出现，所以也许可以选择无糖蛋酒。 （最后一句“Getting at Brown Fat”不太明确在这段语境中的准确含义，可能是一个未完成的表述或者标题性质的内容，暂按字面意思翻译为“针对棕色脂肪”放在最后，仅供参考）