Localization of α-endosulphine in pancreatic somatostatin δ cells and expression during rat pancreas development

Abstract

Aims/hypothesis. α-Endosulphine, a protein that belongs to the cAMP-regulated-phosphoprotein family, has been reported to modulate insulin secretion in vitro through interaction with the pancreatic beta-cell ATP-sensitive potassium (KATP) channel. In this study, we analysed the tissue distribution of α-endosulphine and determined its pancreatic cellular localization. Methods. Quantitative tissue distribution of α-endosulphine was studied by RIA on tissue extracts and cellular/subcellular localization was done using immunocytochemistry, morphometry and western blot analysis. α-Endosulphine and somatostatin release from RINT-3 somatostatin-secreting cells was quantified by RIA. Results. α-Endosulphine, concentrated particularly in the central nervous system, was also detected in a wide variety of tissues including the pancreas. Immunohistochemistry analysis of adult rat pancreatic sections showed that α-endosulphine localized in somatostatin δ cells, where its expression increased during post-natal development. Immunoreactive cells were detected from foetal age E19, and the number of somatostatin cells co-expressing α-endosulphine increased with developmental age from E19 until adult. α-Endosulphine, highly expressed in the cytoplasm of RINT3 somatostatin-secreting cell line, was recovered in the particulate fraction of RINT3 cell extracts but was not co-secreted with somatostatin. Conclusion/interpretation. α-Endosulphine is expressed in all tissues tested including pancreas and is also detected in plasma. Pancreatic α-endosulphine is specifically localized in somatostatin δ cells. This cytosolic protein is not co-secreted with somatostatin and could be physically associated with particulate components of the cells. These findings are not in favour of an endocrine/paracrine effect of α-endosulphine on the beta-cell KATP channel.