类德普西顿刺激3T3-L1脂肪细胞中AKT依赖的葡萄糖摄取
Kanittha Chantarasakha1, Arunrat Yangchum1, Masahiko Isaka1
1National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Phahonyothin Road, Klong Luang, Pathumthani 12120, Thailand.
Journal of natural products
|April 10, 2024
概括
类脱素,特别是来自Aspergillus unguis的尼杜林,增强脂肪细胞中葡萄糖的吸收. 该化合物通过AKT信号传递刺激葡萄糖载体4型 (GLUT4) 转位,为2型糖尿病药物发现提供了潜力.
科学领域:
- 生物化学 生化学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 提高胰岛素敏感组织的葡萄糖吸收对于管理2型糖尿病的高血糖至关重要.
- 菌代谢物代表了针对葡萄糖平衡的新疗法化合物的潜在来源.
研究的目的:
- 调查真菌depsidones在刺激3T3-L1脂肪细胞中葡萄糖吸收中的作用.
- 为了阐明底层分子作用机制的作用,为dpsidone诱导的葡萄糖吸收.
主要方法:
- 从Aspergillus unguis.中分离和识别了西 (尼杜林,诺尼杜林,恩吉诺尔) 的成分.
- 在3T3-L1脂肪细胞中摄取葡萄糖的评估.
- 分析GLUT4表达,AKT和AMPK酸化以及GLUT4转位.
- 评估尼杜林对胰岛素抵抗脂肪细胞的影响.
主要成果:
- 尼杜林,诺尼杜林和恩吉诺尔刺激了脂肪细胞的葡萄糖吸收,尼杜林显示出最显著的效果.
- 尼杜林的葡萄糖吸收增强是剂量和时间依赖的,并增强了胰岛素和甲福林刺激的吸收.
- 尼杜林治疗导致GLUT4表达和AKT和AMPK的酸化增加.
- 抑制AKT酸化,但不抑制AMPK,显著降低了尼杜林诱导的葡萄糖吸收.
- 尼杜林促进了GLUT4转移到血,并增强了胰岛素抵抗脂肪细胞的葡萄糖吸收.
结论:
- 尼杜林主要通过依赖AKT的GLUT4转位来刺激葡萄糖的吸收.
- 尼杜林显示出作为种子化合物的潜力,用于开发治疗2型糖尿病的新药.
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