Researchers test a novel hypothesis to explain the cause of autoimmunity in patients with type 1 diabetes BUMedicine
ible HLA phenotypes and elevated sensitivity to cytokines and free fatty acids . We observed provocative enhanced responsiveness of cultured human fibroblasts from individuals with type 1 diabetes , but not control subjects, to FFA and the inflammatory cytokines TNFα and IL1-β. Major infections increase inflammatory cytokines as well as circulating FFA. Endotoxin-treated animal models of sepsis also exhibit elevated inflammatory cytokines that inhibit FFA oxidation and elevate FFA.
The pancreatic β-cell possesses low reactive oxygen species scavenging capacity and responds to both elevated FFA and cytokines with increased ROS production, a combination that increases exocytosis and trafficking of secretory vesicles to the plasma membrane. Increased trafficking is accompanied by increased cycling of secretory granule proteins and may be linked with increased surface presentation of granule proteins to the immune system.
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