Selenoprotein S (SEPS1) is an antioxidant enzyme that has been shown to protect against oxidative stress (H2O2) induced cell death in a pancreatic β-cell line. We have preliminary data that showed that β-cell specific over-expression of SEPS1 protected against alloxan- and streptozotocin-induced diabetes. Based on these findings, we hypothesised that the deletion of SEPS1 will predispose mice to oxidative stress induced diabetes.
The aim of this study was to generate and characterise pancreatic β-cell specific SEPS1 deleted mice.
Pancreatic β-cell specific SEPS1 deleted mice were generated by Cre-Lox recombination by using RIP-Cre recombinase and fed a standard chow diet. At either eight or sixteen weeks of age, plasma glucose and insulin responses were examined following an intravenous glucose tolerance test (IVGTT).
At eight weeks, mice with a deletion of SEPS1 in the β-cell (-/-) had impaired insulin response (9.3 ± 3.7 vs 60.6 ± 7.0 ng/mL, p < 0.05, n=8-22) associated with reduced insulin levels compared with negative littermates (+/+). At sixteen weeks, this reduced insulin response was persistent (3.4 ± 1.4 vs 15.2 ± 3.5 ng/mL, p < 0.05, n=6-13). This reduction in insulin response was also present when SEPS1 deleted mice were challenged with arginine (86.2 ± 15.4 vs 221.7 ± 43.1 ng/mL, p < 0.05, n=8-9).
In conclusion, the preliminary data suggest that mice with deletion of SEPS1 in β-cells displayed reduced glucose- and arginine- induced insulin secretion. Further studies are warranted to understanding the important role of SEPS1 in the pathogenesis of diabetes.