Phloroglucinol Protects INS-1 Pancreatic β-cells Against Glucotoxicity-Induced Apoptosis

Phytother Res. 2015 Nov;29(11):1700-6. doi: 10.1002/ptr.5407. Epub 2015 Jul 7.

Abstract

Decreasing numbers, and impaired function, of pancreatic β-cells are key factors in the development of type 2 diabetes. This study was designed to investigate whether phloroglucinol protected pancreatic β-cells against glucotoxicity-induced apoptosis using a rat insulinoma cell line (INS-1). High glucose treatment (30 mM) induced INS-1 cell death; however, the level of glucose-induced apoptosis was significantly reduced in cells treated with 100-μM phloroglucinol. Treatment with 10-100-μM phloroglucinol increased cell viability and decreased intracellular levels of reactive oxygen species, nitric oxide, and lipid peroxidation dose-dependently in INS-1 cells pretreated with high glucose. Furthermore, phloroglucinol treatment markedly reduced the protein expression of Bax, cytochrome c, and caspase 9, while increasing anti-apoptotic Bcl-2 protein expression. Cell death type was examined using annexin V/propidium iodide staining, revealing that phloroglucinol markedly reduced high glucose-induced apoptosis. These results demonstrated that phloroglucinol could be useful as a potential therapeutic agent for the protection of pancreatic β-cells against glucose-induced apoptosis.

Keywords: INS-1 pancreatic β-cell; apoptosis; glucotoxicity; phloroglucinol.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose / metabolism
  • Insulin-Secreting Cells / metabolism
  • Insulinoma
  • Lipid Peroxidation*
  • Nitric Oxide / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Phloroglucinol / pharmacology*
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species
  • Nitric Oxide
  • Phloroglucinol
  • Glucose