Awarded an NC3Rs project grant in 2008, Professor Peter Jones, from King’s College London, has improved and validated a pseudoislet model that could replace the use of primary rodent pancreas cells in diabetes research.
Principal Investigator: Peter Jones, Professor of Endocrine Biology
Organisation: King’s College London
Award: £387,732, in 2008, over 36 months
Title: Replacing animal use to study β-cell dysfunction in diabetes
Read more about Professor Jones' research.
The incidence of diabetes is on the increase
There are currently around 2.8 million people in the UK who suffer from diabetes, plus an estimated 850,000 undiagnosed cases. Diabetes is a metabolic disorder affecting glucose metabolism which results from the loss of insulin production in patients with Type I diabetes and insufficient insulin production in patients with Type II diabetes. Type II diabetes accounts for between 85 to 95% of all cases. Its incidence is on the increase correlating with the rise in obesity rates.
At least 50,000 rodents a year are used to provide ß-cells for diabetes research
Insulin is produced and secreted by ß-cells in the pancreas. The ß-cells are arranged in spherical aggregates called the islets of Langerhans, which also contain other endocrine cells. Traditionally studies of ß-cell function have used rodent primary islets of Langerhans, employing a method described over 30 years ago. Rodent and human islets are broadly similar and this research has yielded information on the regulation of insulin synthesis, storage and secretion by normal ß-cells, and on the processes involved in ß-cell pathophysiology. Such studies, however, require large numbers of animals. One rodent pancreas usually provides 200 to 500 islets. For a typical experiment around 100 animals are needed to provide a sufficient number of cells. Since 2000, an average of 500 papers per annum have been published on work using rodent islets; this equates to at least 50,000 rodents each year worldwide.
Many pancreatic cell lines exist but these transformed cells grow as monolayers and lack the differentiated functions of primary islets. They are therefore of limited use for many studies. Previous work by Professor Peter Jones, King’s College London, has shown that when cultured on a gelatinous surface the ß-cell line MIN6 forms islet-like structures termed pseudoislets, which retain the phenotype of ß-cells.
Pseudoislets can replace the use of primary rodent pancreas cells
With NC3Rs funding, Professor Jones has further improved and validated the pseudoislet model as an alternative to the use of primary islets.
Anatomically correct islet-like structures have been assembled from MIN6 cells mixed with glucagon secreting -cells and somatostatin secreting delta cells. These mixed cell pseudoislets closely resemble mouse islets with - and delta cells primarily located in the outer mantle and ß-cells in the inner core. The insulin content and secretion of the ß-cells in pseudoislets in response to glucose stimulation has been shown to be equivalent to primary islets.
Pseudoislets have some advantages over mouse islets because they can be formed using cells which have been experimentally modified to assess the effects of cell/cell interactions on cell function. This has demonstrated the importance of cell adhesion proteins on insulin secretion and that the rate of ß-cell growth is not important in regulating secretory responses. These findings give insights into normal islet function and also enable improvement of the pseudoislet model.
The use of pseudoislets has reduced the use of mice in Professor Jones’ laboratory by approximately 1,000 animals a year.
Pseudosislets are now used across the diabetes research community
Professor Jones has facilitated the adoption of the use of pseudoislets by the wider diabetes research community in the UK and elsewhere in Europe. This included an NC3Rs-sponsored two day workshop in 2010 at King’s College London, attended by ten different research groups. Since then there have been ten publications reporting the use of pseudoislets from the workshop’s participants.
This case study was published in a review of our research portfolio in September 2011.