A Protocol to Enhance INS1E and MIN6 FunctionalityThe Use of Theophylline

Milou Groot Nibbelink*, Giulia Marchioli, Lorenzo Moroni, Marcel Karperien, Aart Van Apeldoorn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In vitro research in the field of type I diabetes is frequently limited by the availability of a functional model for islets of Langerhans. This method shows that by the addition of theophylline to the glucose buffers, mouse insulinoma MIN6 and rat insulinoma INS1E pseudo-islets can serve as a model for islets of Langerhans for in vitro research. The effect of theophylline is dose- and cell line-dependent, resulting in a minimal stimulation index of five followed by a rapid return to baseline insulin secretion by reducing glucose concentrations after a first high glucose stimulation. This protocol solves issues concerning in vitro research for type I diabetes as donors and the availability of primary islets of Langerhans are limited. To avoid the limitations of using human donor material, cell lines represent a valid alternative. Many different cell lines have been reported, but the lack of reproducible responsiveness to glucose stimulation remains a challenge.
Original languageEnglish
Article number1532
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - Sept 2016


  • cell lines
  • insulin secretion in vitro
  • assay methods

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