Hydrogen Sulfide Enhances Pancreatic Beta-Cell Differentiation From Human Tooth Under Normal And Glucotoxic Conditions

Aim: Glucotoxicity obstructs pancreatic differentiation from adult stem cells. The aim was to develop a novel protocol for differentiation of dental pulp stem cells (DPSCs) into pancreatic beta cells and determine the effect of H2S on glucotoxicity. Materials & methods: DPSCs were differentiated with media containing 5.5 or 25.0 mM glucose, exposed to 1 ng/ml H2S. Glucotoxicity, expression of beta-cell markers, INS, PDX1 and GLUT2, and PI3K/AKT pathway were assessed. Results: H2S exposure increased insulin and C-peptide, and protected DPSC-derived pancreatic beta-like cells from glucotoxicity and upregulated INS, PDX1 and GLUT2, and genes of PI3K/AKT pathway. Conclusion: H2S improved effects of glucotoxicity on beta-like cells via PI3K/AKT pathway. The protocol for pancreatic beta-cell differentiation might have applications in regenerative medicine rather than swine pancreas transplantation.