Stanniocalcin-1 Co-Localizes with Insulin in the Pancreatic Islets

Abstract

The polypeptide hormone stanniocalcin-1 (STC-1) is widely expressed in mammals and signals both locally and systemically. In many tissues STC-1 ligand is sequestered by target cell organelles (mitochondria, nuclei, and cholesterol lipid droplets) to exert diverse biological effects. Most notably, STC-1 serves as an uncoupler of oxidative phosphorylation in liver, muscle, and kidney mitochondria. The present paper describes the identification of STC-1 receptors in mouse pancreaticβcells and the discovery that the ligand co-localizes with insulin in pancreaticβcells.In situhybridization (ISH) analysis subsequently revealed that pancreaticβcells were the source of the ligand. Intriguingly however, all ISH signal was localized over putative islet cell nuclei as opposed to the cell cytoplasm. Real-time qPCR and agarose gel electrophoresis revealed that the STC-1 amplicon generated from islet cell total RNA was the same size as that from kidney. However, relative levels of STC-1 gene expression were >100-fold lower in islets than those in kidney tissue. Collectively, these findings are indicative of a local STC-1 signalling pathway in pancreaticβcells. The role of STC-1 in this context remains to be established, but it could very well entail the regulation ofβcell mitochondria membrane potential which is an integral aspect of regulated insulin release. Interestingly, STC-1 immunoreactivity was not evident in embryonic pancreatic islets, suggesting that ligand synthesis may only commence postnatally.