Abstract
Pancreatic islets are endocrine organs that depend on their microvasculature to function. Along with endothelial cells, pericytes comprise the islet microvascular network. These mural cells are crucial for microvascular stability and function, but it is not known if/how they are affected during the development of type 1 diabetes (T1D). Here we investigated islet pericyte density, phenotype and function using living pancreas slices from donors without diabetes, donors with a single T1D-associated autoantibody (GADA+) and recent onset T1D cases. Our data show that islet pericyte and capillary responses to vasoactive stimuli are impaired early on in T1D. Microvascular dysfunction is associated with a switch in the phenotype of islet pericytes towards myofibroblasts. Using publicly available RNAseq data, we further found that transcriptional alterations related to endothelin-1, vascular and ECM remodeling are hallmarks of single Aab+ donor pancreata. Our data show that microvascular dysfunction is present at early stages of islet autoimmunity.
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•Changes in islet pericyte phenotype and function occur during T1D progression.•Vascular responses to vasoactive stimuli are impaired in islets from Aab+ and T1D donors.•Changes related to ET-1 action/signaling are found in Aab+ and T1D islet vascular cells.•Vascular and ECM remodeling occur in Aab+ and T1D donor pancreata.
Mateus Gonçalves et al. found that islet pericytes and capillaries are dysfunctional at early stages of islet autoimmunity. Several alterations related to endothelin-1 signaling, vascular and ECM remodeling are present in single Aab+ donor pancreata, supporting the involvement of the vasculature in type 1 diabetes pathogenesis.
