Mitochondrial and protein homeostasis pathways are transcriptionally impaired in islets during type 1 diabetes pathogenesis
The decline in first-phase insulin response (FPIR) during the presymptomatic period of type 1 diabetes (T1D) is well established. In-situ functional studies with pancreas tissue slices showed that {beta}-cell loss of glucose-responsiveness was independent of T-cell infiltration into islets in recent-onset T1D cases. However, the mechanisms driving {beta}-cell dysfunction before the onset of T1D…
Type 1 diabetes (T1D) research has revealed that mitochondrial and protein homeostasis pathways in islets are transcriptionally impaired during the disease's progression. An in-situ, whole-islet phenotypical and transcriptomic approach was used to study pancreas tissue from donors at various stages of T1D. The findings showed that both autoantibody positive (single or multiple) donors and T1D patients exhibited disrupted protein translation, processing in the endoplasmic reticulum (ER), and ER stress.
Additionally, these islets showed activation of post-transcriptional gene regulation and mitochondrial metabolic dysfunction. These impaired mechanisms were consistently observed across multiple AAb+ donors and T1D patients with varying disease durations.
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