Differences in ß-cell Maturity Are Important for Effective Insulin Production

Publishing their findings in Nature Communications, researchers from the University of Birmingham reveal that subtle differences in the levels of PDX1 and MAFA proteins, and more broadly, differences in β-cell maturity, contribute to how clusters of insulin-producing cells, known as islets, function.

"Our research shows that differences in β-cell maturity, defined using PDX1 and MAFA levels, are needed across the islet for proper insulin release,” says corresponding author David Hodson.  “Unexpectedly, an increase in the proportion of mature β-cells, is associated with islet failure. It seems that, rather like society, the islet needs cells with all ages to be properly functional.”

Normally, mature and immature β-cells co-exist within the adult islet and can be grouped into subpopulations according to differences in their levels of specific genes and proteins. Immature β-cells are generally considered to be poorly functional when viewed alone, as single cells.

"Redressing the balance between immature and mature β-cells restores islet function under conditions of metabolic stress‚an excess of sugar and fat in the diet—providing evidence that both 'weak' and 'strong' β-cells could contribute to proper islet function and insulin release,” he adds. 

Researchers also found that islets containing proportionally more PDX1HIGH and MAFAHIGH β-cells showed defects in cell function (metabolism, ionic fluxes and insulin secretion). The team believes maintaining a mix of 'strong' and 'weak' β-cells is important for effective insulin production.