[Toxic effect of immunosuppression agent Everolimus on insuloma cells and pancreatic islets of SD rat]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2010 Jan;41(1):68-72.
[Article in Chinese]

Abstract

Objective: To investigate the effect of immunosuppression agent Everolimus on the viability and function of insuloma cells (INS-1) and pancreatic islet cells cultured in vitro.

Methods: INS-1 cells and islets were treated with a series of concentrations of immunosuppression agents (Everolimus, Cyclosporin A, Sirolimus and Mycophenolate Mofetil). The viability of INS-1 cells and rat pancreatic islets were determined with MTT and the function of INS-1 cells and rat pancreatic islets was evaluated with Glucose-stimulated insulin secretion assay.

Results: Above the clinical blood concentration, the inhibition rate of islet cell proliferation in the high concentration group of Everolimus and Sirolimus was significantly lower than that of Cyclosporin A and Mycophenolate Mofetil group (P < 0.05); Everolimus in the blood drug level, like other immunosuppressive agents, can inhibit the function of insulin secretion, and the stimulation index of each group was no significant difference.

Conclusion: Compared to Mycophenolate Mofetil and Cyclosporin A, Everilimus and Sirolimus demonstrate lower toxicity effect on INS-1 cells and rat pancreatic islets in vitro and Everolimus is expected as a new type of immunosuppressive agent used in clinical islet transplantation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival
  • Cells, Cultured
  • Cyclosporine / adverse effects
  • Cyclosporine / pharmacology
  • Everolimus
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacology*
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulinoma / pathology*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / pharmacology
  • Pancreatic Neoplasms / pathology
  • Rats
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / pharmacology

Substances

  • Immunosuppressive Agents
  • Insulin
  • Cyclosporine
  • Everolimus
  • Mycophenolic Acid
  • Sirolimus