Insulin Derived Fibrils Induce Cytotoxicity and Trigger Inflammation in Murine Models.

BACKGROUND

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.

METHOD

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.

RESULTS

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 .

CONCLUSIONS

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.