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bioRxiv · 10.1101/2025.01.29.635550

Proinflammatory cytokines mediate pancreatic beta-cell specific alterations to Golgi morphology via iNOS-dependent mitochondrial inhibition

Blom, S. E.·Behan-Bush, R. M.·Ankrum, J. A.·Yang, L.·Stephens, S. B.
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Abstract

Type 1 diabetes (T1D) is caused by the selective autoimmune ablation of pancreatic {beta}-cells. Emerging evidence reveals {beta}-cell secretory dysfunction arises early in T1D development and may contribute to diseases etiology; however, the underlying mechanisms are not well understood. Our data reveal that proinflammatory cytokines elicit a complex change in the {beta}-cells Golgi structure and function. The structural modifications include Golgi compaction and loss of the inter-connecting ribbon resulting in Golgi fragmentation. Our data demonstrate that iNOS generated nitric oxide (NO) is necessary and sufficient for {beta}-cell Golgi re-structuring. Moreover, the unique sensitivity of the {beta}-cell to NO-dependent mitochondrial inhibition results in {beta}-cell specific Golgi alterations that are absent in other cell types, including -cells. Collectively, our studies provide critical clues as to how {beta}-cell secretory functions are specifically impacted by cytokines and NO that may contribute to the development of {beta}-cell autoantigens relevant to T1D.

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Blom, S. E., Behan-Bush, R. M., Ankrum, J. A., Yang, L., Stephens, S. B.. 2025-01-29. Proinflammatory cytokines mediate pancreatic beta-cell specific alterations to Golgi morphology via iNOS-dependent mitochondrial inhibition. https://doi.org/10.1101/2025.01.29.635550

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