Apigenin Enhances the Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells Into Insulin-Producing Cells...

The present study aimed to evaluate the effect of apigenin (Api) on the differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) into insulin-producing cells (IPCs) via inducing autophagy. ASCs were isolated from fresh adipose tissues using mechanical and enzymatic digestion and characterized using flow cytometry. ASCs were treated with Api (0, 5, 10, 25, and 50 µM) for 48 and 72 h, to determine the Api optimum dose using the MTT test. ASCs were exposed to optimal Api doses (5 and 10 µM) and differentiated into IPCs by cultivating them in a differentiation medium in a two-step manner. The expression of IPC and autophagy genes and proteins was evaluated using real-time PCR and Western blot, and glucose-stimulated insulin and C-peptide secretion were assessed using colorimetric methods. Autophagy and β cell-specific protein interactions were analyzed using the STRING database. 94% of ASCs expressed CD73, CD90, and CD105, while 99% didn't express CD34 and CD45. Api treatment increased the expression of PDX1, GLUT2, Insulin, LC3A, ATG5, and ATG7 genes, as well as LC3-1 and LC3-II proteins in a dose-dependent manner. Glucose-stimulated insulin and C-peptide secretion were significantly higher in Api-treated groups. Bioinformatic analysis revealed that MAPK and FOXO3 were central proteins that interacted with and connected β cell-specific and autophagy functional clusters. Api increased the differentiation of ASCs into IPCs by inducing autophagy and can be considered a novel strategy for enhancing differentiation efficiency.