Biology subjects

Blom, S. E.

Publications and source records attributed to Blom, S. E..

2 recordsLinked to original sources

bioRxiv2025

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

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.

cell biology↗

bioRxiv2021

Hyperglycemia-induced alteration of ER redox homeostasis delays ER export of proinsulin

Defects in the pancreatic {beta}-cells secretion system are well-described in Type 2 diabetes (T2D) and include impaired proinsulin processing and a deficit in mature insulin-containing secretory granules; however, the cellular mechanisms underlying these defects and the contribution of hyperglycemia to this process remain poorly understood. Here, we used an in situ fluorescent pulse-chase strategy and proximity labeling-based quantitative proteomics analysis to study proinsulin trafficking and demonstrate a direct link to glucose metabolism via the production of redox intermediates that facilitate proinsulin export from the ER. We show that ER export of proinsulin is delayed in T2D models resulting in decreased insulin granule formation and further demonstrate this process can be regulated by NADPH and reducing equivalent availability. Together, these data highlight a critical role for nutrient metabolism and mitochondrial dysfunction in the maladaptive remodeling of the {beta}-cells secretory pathway in the decline of {beta}-cell function in T2D.

cell biology↗