Microvascular homeostasis is compromised in pancreatic islets in a mouse model of beta cell loss and low-grade inflammation.

Vascular dysfunction is considered a consequence of diabetes. However, in pancreatic islets, some haemodynamic changes occur before the onset of symptoms. The underlying mechanisms driving islet vascular abnormalities have not been fully characterized, but islet pericyte dysfunction appears to be an early event in the pathogenesis of human type 1 diabetes (T1D). It remains to be investigated, however, how abnormal pericyte physiology affects their ability to regulate islet blood flow and vascular permeability. To address this issue, we treated mice with multiple subdiabetogenic doses of the beta cell toxin streptozotocin (STZ; 50mg/kg) and recorded islet vascular responses when animals developed glucose intolerance but were still not diabetic (average fed glycemia <200 mg/dL). At this stage, accompanying increased macrophage density, islet pericytes adopted a myofibroblast-like appearance and interacted closely with endothelial cells expressing high levels of the adhesion molecule ICAM-1. This phenotypical switch of pericytes in STZ-treated mice had functional repercussions: it impacted glucose-induced vasomotor responses Article highlights: Functional and morphological alterations of islet capillaries occur in mice early after multiple low dose STZ treatment;Islet pericytes remodel and express higher levels of the myofibroblast marker periostin upon STZ treatment; Islet pericyte cytosolic Ca