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Type 1 diabetes (T1D) has historically been framed as a disease initiated and maintained by dysregulated immunity that targets insulin producing β-cells. However, recent findings from human tissue analysis, single cell transcriptomics, and longitudinal cohort studies reveal that intrinsic β-cell stress responses contribute substantially to early disease development. These responses include endoplasmic reticulum stress, remodeling of the unfolded protein response, oxidative and metabolic strain, impaired proinsulin folding and processing, altered granule biogenesis, increased production of cytokines and chemokines, and significant enhancement of antigen presentation pathways. Together, these stress responses create a cellular environment that increases immunogenicity and influences the recruitment and activation of immune cells. This perspective provides a comprehensive integration of mechanistic and clinical evidence showing that β-cell intrinsic biology interacts closely with immune dysregulation to shape disease trajectory. Mechanistic insights from human islets are integrated with translational data from longitudinal clinical studies, revealing a coherent model in which β-cell stress appears early, informing biomarker patterns, influences disease heterogeneity, and provides promising therapeutic targets. This overview offers a unified, balanced conceptual framework to guide future research, early detection strategies, and treatment development.