Phogrin Regulates High-Fat Diet-Induced Compensatory Pancreatic β-Cell Growth by Switching Binding Partners

• Published in: Nutrients 2024-01, Vol.16 (1), p.169
• Main Authors: Kubota, Chisato, Torii, Ryoko, Hosaka, Masahiro, Takeuchi, Toshiyuki, Gomi, Hiroshi, Torii, Seiji
• Format: Article
• Language: English
• Subjects: Antibodies; Aprotinin; Cell growth; Cloning; Dextrose; Diabetes; Diet; Ethylenediaminetetraacetic acid; Glucose; Growth; high-fat diet; Insulin; insulin receptor substrate; Insulin resistance; insulin signaling; islet antigen; Laboratories; Pancreatic beta cells; pancreatic β-cell mass; Phosphatase; Phosphatases; Proteins; secretory granules; Signal transduction; Type 2 diabetes; Tyrosine
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16010169

The receptor protein tyrosine phosphatase phogrin primarily localizes to hormone secretory granules in neuroendocrine cells. Concurrent with glucose-stimulated insulin secretion, phogrin translocates to pancreatic β-cell plasma membranes, where it interacts with insulin receptors (IRs) to stabilize insulin receptor substrate 2 (IRS2) that, in turn, contributes to glucose-responsive β-cell growth. Pancreatic β-cell development was not altered in β-cell-specific, phogrin-deficient mice, but the thymidine incorporation rate decreased in phogrin-deficient islets with a moderate reduction in IRS2 protein expression. In this study, we analyzed the β-cell response to high-fat diet stress and found that the compensatory expansion in β-cell mass was significantly suppressed in phogrin-deficient mice. Phogrin-IR interactions occurred only in high-fat diet murine islets and proliferating β-cell lines, whereas they were inhibited by the intercellular binding of surface phogrin under confluent cell culture conditions. Thus, phogrin could regulate glucose-stimulated compensatory β-cell growth by changing its binding partner from another β-cell phogrin to IR in the same β-cells.