Abstract
ABSTRACT. Background. Clinical outcome after pancreatic islet transplantation therapy of T1D has improved, but long-term results are not optimal. During isolation the islets are exposed to hypoxia due to disruption of the vascularized environment in situ. In this study we investigated the effect of 3 hours exposure of hypoxia on viability, function and inflammation in isolated pancreatic islets from mice in vitro. Materials and methods. Isolated pancreatic islets from mice were divided into two groups; one group was exposed to 3 hours of hypoxia (1 % O2) and the other group was exposed to 3 hours of normoxia (21 % O2) and served as control. The islets function were investigated by glucose stimulated insulin secretion challenge and insulin secretion were measured using insulin ELISA. The viability was measured by quantifying intracellular histone fragments and ATP. The inflammatory mediators IL-6 and MIP-2 were quantified from cell free supernatant. Results. The secretion of insulin in islets exposed to hypoxia was significantly reduced compared to controls; (n=4, p=0,01). The islets viability was reduced measured by increased cell death and reduced ATP content compared to the controls; (n=4, p=0,04), (n=4, p=<0,0001). There was a significantly increased secretion of MIP-2 and a tendency to increased IL-6 compared to controls; (n=4, p=0,03), (n=4, p=0,4). Conclusion. The result shows that 3 hours of hypoxia reduces the function and viability, and increases the inflammation in the islets. Interventions that reduce hypoxia could therefore be an important strategy to improve the survival and quality of the islets in the preculture period prior to transplantation.