PTHrP increases pancreatic β-cell-specific functions in well-differentiated cells

Abstract Parathyroid hormone-related protein (PTHrP) is reportedly produced in normal islets and insulinomas. PTHrP induces differentiation in some cell-types and growth in others. We examined whether PTHrP production is greater in well-differentiated or growing β cells and whether PTHrP induces differentiation or growth in β cells. We used four groups of the well-differentiated mouse β cell line MIN6 with 17, 25, 31 and 41 passages, and mouse pancreatic islets. With passage, insulin content diminished, whereas the expression of PTHrP, its activating enzyme furin and cell growth gradually increased. PTHrP increased insulin content and mRNA levels more in MIN6-17 cells than in MIN6-41 cells. In contrast, PTHrP increased DNA synthesis more extensively in MIN6-41 cells than in MIN6-17 cells. Dibutyryl cAMP reproduced PTHrP's effect on insulin content and DNA synthesis. We conclude that PTHrP increases insulin expression in well-differentiated β cells through the cAMP pathway and stimulates growth in growing β cells.