Optical Nanoscopy of Cytokine-Induced Structural Alteration of Endoplasmic Reticulum and Golgi Apparatus in Insulin Secreting Cells

Pro-inflammatory cytokines play a role in the failure of β-cells in type 1 and type 2 diabetes. While existing data from ‘omics’ experiments allow for some understanding of the molecular mechanisms behind cytokine-induced dysfunction in β-cells, no report thus far has provided information on the direct imaging of the β-cell landscape with nanoscale resolution following cytokine exposure. In this study, we use Airyscan-based optical super-resolution microscopy of Insulinoma 1E (INS-1E) cells to investigate the structural properties of two subcellular membranous compartments involved in the production, maturation and secretion of insulin-containing granules, the Endoplasmic Reticulum (ER) and the Golgi Apparatus (GA). Our findings reveal that exposure of INS-1E cells to IL-1β and IFN-γ for 24 hours leads to significant structural alterations of both compartments. In more detail, both ER and GA fragment and give rise to vesicle-like structures with markedly reduced characteristic area and perimeter and increased circularity with respect to the original structures. These findings complement the molecular data collected thus far on these compartments and their role in β-cell dysfunction using and lay the ground for future optical-microscopy-based ex-vivo and in-vivo investigations.