Selenocysteine insertion sequence binding protein 2 (Sbp2) in the sex-specific regulation of selenoprotein gene expression in mouse pancreatic islets

Abstract

Selenoproteins are a group of selenocysteine-containing proteins with major roles in cellular antioxidant defense and thyroid hormone metabolism. Selenoprotein expression is determined by hierarchical mechanisms that result in tissue-specific levels. Current data inadequately explain the abundance of various selenoproteins under normal and pathological conditions, including in pancreatic β-cells. Selenocysteine insertion sequence binding protein 2 (SBP2) is a critical protein in selenoprotein translation that also plays an essential role in stabilizing selenoprotein transcripts by antagonizing nonsense-mediated decay (NMD). Importantly, dysfunctional SBP2 is associated with endocrine disorders in humans. Here we describe the impact of induced Sbp2 deficiency in pancreatic β-cells on selenoprotein transcript profiles in the pancreatic islets of C57BL/6J mice. Sex differences were noted in control mice, in which female islets showed 5 selenoproteins decreased and one increased versus male islets. Induced Sbp2 deficiency in pancreatic β-cells altered expression of only 3 selenoprotein transcripts in male islets, whereas 14 transcripts were reduced in female islets. In all cases, decreased transcription was observed in genes known to be regulated by NMD. The differential impact of Sbp2 deletion on selenoprotein transcription between sexes suggests sex-specific hierarchical mechanisms of selenoprotein expression that may influence islet biology and consequentially metabolic disease risk.

Selenomethionine modulates insulin secretion in the MIN6‐K8 mouse insulinoma cell line

“…In vivo, Gpx3 is the only extracellular subtype of the Gpx family, and it is most highly expressed by kidney [47]; however, it is also highly expressed in the pancreas, lung, heart, liver, and skeletal muscle [47]. In a gene expression analysis of mouse islets, Gpx3 was the most highly expressed selenoprotein transcript in both males and females [48]. Several clinical trials had reported single-nucleotide polymorphisms (SNP) in the Gpx3 gene promoter region are associated with cardiovascular disease [49][50][51].…”