The role of noggin in regulation of high glucose-induced apoptosis and insulin secretion in INS-۱ rat beta cells

Objective(s):The purpose of this study was to investigate the effects of Noggin on high glucose-induced apoptosis and insulin secretion in pancreatic beta cells. Materials and Methods: Different concentrations of glucose were used to examine their effects on INS-۱ rat beta cells in vitro. When specific siRNA targeting Noggin and recombinant Noggin were added, apoptosis and insulin secretion were measured, respectively to determine their effects in INS-۱ cells. Results: Glucose stimulated the expression of Noggin in a dose-dependent manner. Knockdown of Noggin further increased apoptosis and reduced insulin secretion when INS-۱ cells were exposed to high glucose. Conversely, administration of recombinant Noggin significantly reduced apoptotic cell number, and promoted insulin secretion. Finally, treatment with inhibitor of Smad phosphorylation exerted similar effects on cell apoptosis and insulin production to Noggin administration in glucose-treated INS-۱ cells. Conclusion: Our findings indicate that Noggin inhibits apoptosis and promotes insulin secretion in pancreatic beta cells through the inhibition of Smad signaling. Gene therapy of delivering Noggin may facilitate the treatment for patients with type ۲ diabetes mellitus.

Keywords:

Apoptosis , Insulin , Noggin , Pancreatic beta cell , Smad , Type ۲ diabetes mellitus