Abstract:
Laboratory-based research aimed at understanding processes regulating insulin secretion and mechanisms underlying
β-cell dysfunction and loss in diabetes often makes use of rodents, as these processes are in many respects similar between
rats/mice and humans. Indeed, a rough calculation suggests that islets have been isolated from as many as 150,000 rodents
to generate the data contained within papers published in 2009 and the first four months of 2010. Rodent use for islet
isolation has been mitigated, to a certain extent, by the availability of a variety of insulin-secreting cell lines that are used
by researchers world-wide. However, when maintained as monolayers the cell lines do not replicate the robust, sustained
secretory responses of primary islets which limits their usefulness as islet surrogates. On the other hand, there have been
several reports that configuration of MIN6 β-cells, derived from a mouse insulinoma, as three-dimensional cell clusters
termed ‘pseudoislets’ largely recapitulates the function of primary islet β-cells. The Diabetes Research Group at King’s College
London has been using the MIN6 pseudoislet model for over a decade and they hosted a symposium on “Pseudoislets as
primary islet replacements for research”, which was funded by the UK National Centre for the Replacement, Refinement and
Reduction of Animals in Research (NC3Rs), in London on 15th and 16th April 2010. This small, focused meeting was conceived
as an opportunity to consolidate information on experiences of working with pseudoislets between different UK labs, and
to introduce the theory and practice of pseudoislet culture to laboratories working with islets and/or β-cell lines but who do
not currently use pseudoislets. This short review summarizes the background to the development of the cell line-derived
pseudoislet model, the key messages arising from the symposium and emerging themes for future pseudoislet research