Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor

摘要: Background Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, DPP-IV inhibitor, on β-cell regeneration in diabetic mice. Materials & Methods Diabetes C57BL/6 mice was induced streptozotocin. PSN632408 sitagliptin alone or combination were administered to for 7 weeks along BrdU daily. Nonfasting blood glucose levels monitored. After treatment, oral tolerance test (OGTT), plasma active levels, mass α- replication, neogenesis evaluated. Results Normoglycemia not achieved vehicle-treated mice. By contrast, 32% (6 19) PSN632408-treated mice, 36% (5 14) sitagliptin-treated 59% (13 22) treated normoglycemia after treatment. Combination therapy significantly increased improved clearance, stimulated both augmented mass. Furthermore, treatment from pancreatic duct-derived cells. Conclusion Our results demonstrate that agonist inhibitor may offer novel therapeutic strategy stimulating reversing diabetes.