Mouse study implicates STEAP2 in glucose-stimulated insulin secretion

Researchers have posted a preprint on bioRxiv showing that the protein STEAP2 — encoded by a gene whose locus is associated with altered glycaemic traits and type 2 diabetes risk in genome-wide association studies — is required for normal glucose-stimulated insulin secretion in mice.

Using CRISPR-Cas9-assisted homologous recombination, the team generated mice carrying a conditional null allele for Steap2 (Steap2fl/fl) and crossed these animals to a line expressing Cre recombinase under the rat insulin promoter, thereby deleting Steap2 specifically in pancreatic beta-cells. The resulting animals showed impaired insulin secretion in response to glucose challenge, providing direct functional evidence that this locus influences beta-cell physiology rather than another metabolic tissue.

Steap2 encodes Six-transmembrane epithelial antigen of the prostate-2, a protein with roles in metal ion transport and endosomal trafficking whose function in the pancreas had not previously been established. Type 2 diabetes is influenced by common variants distributed across hundreds of loci, most of which remain functionally uncharacterised. This work represents a step towards closing that gap for one such locus, though as a preprint the findings await peer review and replication. The study is of primary interest to researchers working in diabetes genetics and islet biology, and connects naturally to recent single-cell eQTL work in the human pancreas published on Genetic Current.