Hydrogen sulfide enhances pancreatic β-cell differentiation from human tooth under normal and glucotoxic conditions

Regen Med. 2017 Mar;12(2):125-141. doi: 10.2217/rme-2016-0142. Epub 2016 Dec 7.


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 β 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 β-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 β-like cells from glucotoxicity and upregulated INS, PDX1 and GLUT2, and genes of PI3K/AKT pathway.

Conclusion: H2S improved effects of glucotoxicity on β-like cells via PI3K/AKT pathway. The protocol for pancreatic β-cell differentiation might have applications in regenerative medicine rather than swine pancreas transplantation.

Keywords: glucotoxicity; hydrogen sulfide; pancreatic β-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Dental Pulp / drug effects
  • Dental Pulp / metabolism
  • Glucose / adverse effects*
  • Humans
  • Hydrogen Sulfide / pharmacology*
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Organogenesis / drug effects
  • Organogenesis / physiology
  • Oxidants / pharmacology
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • Sweetening Agents / adverse effects
  • Tooth / cytology*
  • Tooth / drug effects
  • Tooth / metabolism


  • Biomarkers
  • Insulin
  • Oxidants
  • Sweetening Agents
  • Glucose
  • Hydrogen Sulfide