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

first_pagesettingsOrder Article Reprints Open AccessArticle Optical Nanoscopy of Cytokine-Induced Structural Alterations of the Endoplasmic Reticulum and Golgi Apparatus in Insulin-Secreting Cells by Licia Anna Pugliese 1,*,Valentina De Lorenzi 1ORCID,Marta Tesi 2,Piero Marchetti 2 andFrancesco Cardarelli 1,*ORCID 1 NEST Laboratory—Scuola Normale Superiore, Piazza San Silvestro 12, 56127 Pisa, Italy 2 Islet Cell Laboratory, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy * Authors to whom correspondence should be addressed. Int. J. Mol. Sci. 2024, 25(19), 10391; https://doi.org/10.3390/ijms251910391 Submission received: 9 August 2024 / Revised: 20 September 2024 / Accepted: 25 September 2024 / Published: 27 September 2024 (This article belongs to the Section Molecular Biology) Downloadkeyboard_arrow_down Browse Figures Versions Notes Abstract 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 h leads to significant structural alterations of both compartments. In more detail, both the ER and the 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 and lay the groundwork for future optical microscopy-based ex vivo and in vivo investigations.