Parathyroid Hormone–Related Protein Enhances Human -Cell Proliferation and Function With Associated Induction of Cyclin-Dependent Kinase 2 and

OBJECTIVE—Inducing human -cell growth while enhancing function is a major goal in the treatment of diabetes. Parathyroid hormone–related protein (PTHrP) enhances rodent -cell growth and function through the parathyroid hormone-1 receptor (PTH1R). Based on this, we hypothesized that PTH1R is ex-pressed in human -cells and that PTHrP has the potential to enhance human -cell proliferation and/or function. RESEARCH DESIGN AND METHODS—PTH1R expression, -cell proliferation, glucose-stimulated insulin secretion (GSIS), and expression of differentiation and cell-cycle genes were analyzed in human islets transduced with adenoviral PTHrP constructs or treated with PTHrP peptides. The effect of overex-pression of late G1/S cell cycle molecules was also assessed on human -cell proliferation. RESULTS—We found that human -cells express PTH1R. Mor