内毒素加速胰岛素粉样蛋白的形成,并使胰岛素信号传导不活化
Qin-Yu Meng1, Zhong-Xia Lu1, Lu-Xin Liu1
1Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Life sciences
|November 10, 2023
概括
内毒素加速胰岛素粉样蛋白的形成,破坏其结构并降低有效性. 这影响了治疗性胰岛素的制备,储存和胰岛素抵抗研究.
科学领域:
- 生物化学 生物化学
- 材料科学 材料科学 材料科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 治疗性胰岛素对于糖尿病管理至关重要.
- 胰岛素粉样蛋白的形成可能会影响其有效性和安全性.
- 内毒素是生物制剂中常见的污染物.
研究的目的:
- 为了研究内毒素对胰岛素粉样蛋白形成的影响.
- 了解内毒素如何影响胰岛素的结构和功能.
- 为安全的胰岛素制备和储存提供指导.
主要方法:
- 提奥夫拉T (ThT) 和ANS结合试验用于研究粉样蛋白形成动力学.
- 扫描电子显微镜 (SEM) 和传输电子显微镜 (TEM) 用于纤维状形态学.
- 循环二元化 (CD),FTIR和拉曼光谱用于结构分析.
- 细胞活力测试 (cck-8) 和胰岛素信号通路分析,以评估细胞毒性和疗效.
主要成果:
- 内毒素显著加快胰岛素纤维素的形成,以剂量依赖的方式.
- 暴露于内毒素导致胰岛素的疏水性增加和二次结构改变 (α-螺旋向β-链过渡).
- 在内毒素存在的情况下,SEM和TEM显示出更密集,更厚的胰岛素纤维素.
- 寡合和氨基原型胰岛素聚合物都具有细胞毒性,寡合物更强效.
- 用内毒素治疗的胰岛素在激活胰岛素信号传递方面有效性降低.
结论:
- 内毒素破坏胰岛素的结构完整性,促进氨基粉症并降低其治疗效果.
- 这些发现强调了内毒素控制在胰岛素制备和储存中的重要性.
- 这项研究表明,内毒素诱导的胰岛素变化与胰岛素抵抗之间存在潜在的联系.
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