Proinflammatory Cytokines Mediate Pancreatic β-Cell-Specific Alterations to Golgi Integrity via iNOS-Dependent Mitochondrial Inhibition.

ABSTRACT: Type 1 diabetes (T1D) is caused by the selective autoimmune ablation of pancreatic β-cells. Emerging evidence reveals β-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 β-cell's Golgi structure and function. The structural modifications include Golgi compaction and loss of the interconnecting ribbon resulting in Golgi fragmentation. We further show that Golgi structural alterations coincide with persistent altered cell surface glycoprotein composition. Our data demonstrate that inducible nitric oxide synthase (iNOS)-generated nitric oxide (NO) is necessary and sufficient for β-cell Golgi restructuring. M

SUBMITTER: Blom SE 

PROVIDER: S-EPMC12585162 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature