Department of Biomedical Engineering, Integrative Biosciences Center. Wayne State University, Detroit, MI, USA.
Department of Surgery, School of Medicine. University of Connecticut, Farmington, CT, USA.
J Diabetes Sci Technol. 2023 Jan;17(1):163-171. doi: 10.1177/19322968211033868. Epub 2021 Jul 21.
Effective exogenous insulin delivery is the cornerstone of insulin dependent diabetes mellitus management. Recent literature indicates that commercial insulin-induced tissue reaction and cellular cytotoxicity may contribute to variability in blood glucose as well as permanent loss of injection or infusion site architecture and function. It is well accepted that insulin formulations are susceptible to mechanical and chemical stresses that lead to insulin fibril formation. This study aims to characterize and toxicity, as well as pro-inflammatory activity of insulin fibrils.
cell culture evaluated cytotoxicity and fibril uptake by macrophages and our modified murine air-pouch model quantified inflammatory activity. The latter employed FLOW cytometry and histopathology to characterize fibril-induced inflammation , which included fibril uptake by inflammatory phagocytes.
These studies demonstrated that insulin derived fibrils are cytotoxic to cells . Furthermore, inflammation is induced in the murine air-pouch model and in response, macrophages uptake fibrils both and .
Administration of insulin fibrils can lead to cytotoxicity in macrophages. data demonstrate insulin fibrils to be pro-inflammatory which over time can lead to cumulative cell/tissue toxicity, inflammation, and destructive wound healing. Long term, these tissue reactions could contribute to loss of insulin injection site architecture and function.
有效的外源性胰岛素输送是胰岛素依赖型糖尿病管理的基石。最近的文献表明，商业胰岛素引起的组织反应和细胞毒性可能导致血糖变化以及注射或输注部位结构和功能的永久性丧失。人们普遍认为胰岛素制剂容易受到机械和化学压力的影响，从而导致胰岛素纤维的形成。本研究旨在对胰岛素纤维的理化性质、细胞毒性以及促炎活性进行表征。
细胞培养评估了巨噬细胞的细胞毒性和纤维摄取，我们改良的鼠气囊模型定量评估了炎症活性。后者采用流式细胞术和组织病理学来描述纤维诱导的炎症，包括炎症吞噬细胞对纤维的摄取。
这些研究表明，胰岛素衍生的纤维对细胞具有细胞毒性。此外，在鼠气囊模型中诱导了炎症，并且巨噬细胞摄取纤维，无论是在体外还是体内。
胰岛素纤维的给药可导致巨噬细胞的细胞毒性。数据表明胰岛素纤维具有促炎作用，随着时间的推移，可能导致累积的细胞/组织毒性、炎症和破坏性的伤口愈合。从长远来看，这些组织反应可能导致胰岛素注射部位结构和功能的丧失。
