FGF1的内分泌产生一种新型和强大的胰岛素敏感剂
Jae Myoung Suh1, Johan W Jonker2, Maryam Ahmadian3
11] Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA [2].
Nature
|July 22, 2014
概括
纤维细胞生长因子1 (FGF1) 的使用有效降低了糖尿病小鼠的葡萄糖. 这种新疗法可以增强胰岛素敏感性,没有常见的副作用,为2型糖尿病治疗提供了新的希望.
科学领域:
- 代谢研究的研究.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 纤维细胞生长因子1 (FGF1) 主要是一种自身蛋白/副蛋白调节剂,通常与蛋白质甘结合,限制其循环.
- 虽然FGF1具有众所周知的mitogenic特性,但高脂肪饮食中的FGF1淘汰小鼠的胰岛素耐药性表明FGF1在营养稳定中的作用.
研究的目的:
- 研究复合FGF1 (rFGF1) 在治疗胰岛素耐药性和2型糖尿病方面的治疗潜力.
- 为了确定FGF1的降血糖效应是否可以与其致性活性分开.
主要方法:
- 对糖尿病小鼠进行单剂rFGF1的亲肠道注射.
- 使用rFGF1.1.的慢性药理治疗.
- 评估葡萄糖水平,胰岛素依赖的葡萄糖摄取量,肝脏葡萄糖的产生,以及体重增加和肝脏肥胖症等副作用.
- 对FGF受体1信号通路的分析.
主要成果:
- 一次剂量rFGF1诱导了强效的,剂量依赖的,胰岛素依赖的降血糖,而不会导致低血糖.
- 慢性rFGF1治疗通过增加骨肌肉的葡萄糖吸收和减少肝脏的葡萄糖生产,改善了全身的胰岛素敏感性.
- rFGF1治疗没有导致诸如体重增加,肝脏肥胖症或骨质损失等不良影响.
- 降血糖效应与中毒性活性分离,主要通过FGF受体1信号介导.
结论:
- 外源性,非菌原性FGF1表现出一种新的胰岛素敏感作用,具有治疗胰岛素抵抗和2型糖尿病的治疗潜力.
- FGF1代表了代谢障碍的一种有前途的治疗药物,在没有当前治疗的副作用的情况下提供了好处.
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