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 previously shown that β-cell specific over-expression of SEPS1 protected against alloxan- and streptozotocin-induced diabetes suggesting that SEPS1 may play a critical role in the regulation of β-cell function. With reference to 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 eight and sixteen weeks of age, plasma glucose and insulin responses were examined following an intravenous glucose tolerance test (IVGTT) and an oral glucose tolerance test (OGTT) in deleted mice and negative littermates.
At eight weeks of age, mice with a partial deletion of SEPS1 in the β-cell (+/-) had reduced glucose-mediated insulin response (32.35 ± 9.23 vs 73.73 ± 8.92 ng/mL, p < 0.05, n=15-29) associated with impaired glucose tolerance compared with negative littermates (+/+). At sixteen weeks of age, this reduced insulin response was persistent (11.82 ± 2.29 vs 24.13 ± 5.55 ng/mL, p < 0.05, n=10). Surprisingly, SEPS1 deleted (+/-) mice showed better glucose tolerance (173.50 ± 129.51 vs 584.63 ± 55.40 mmol/L, p < 0.05, n=3-10) compared with negative littermates.
In conclusion, our data suggest the mice with a partial deletion of SEPS1 in the β-cell displayed reduced insulin secretion and better glucose tolerance, suggesting compensated insulin sensitivity. Further studies are warranted to understand the role of β-cell SEPS1 in glucose tolerance.