When blood sugar levels rise after eating, cells in the pancreas called β-cells normally respond by releasing insulin, which in turn stimulates cells to start absorbing sugars. In people with diabetes, this system breaks down, leading to high blood sugar levels that can damage the body and causes illness.
In type 1 diabetes, the immune system attacks and destroys β-cells; in type 2, the β-cells do not produce enough insulin, or the body becomes resistant to insulin.
Scientists have previously shown in mouse studies that if β-cells are destroyed, another type of pancreatic cell, called α-cells become more β-like and start making insulin. These α-cells normally produce the hormone glucagon, and are found alongside β-cells in clumps of hormone-secreting cells called pancreatic islets or islets of Langerhans. Previous studies showed that two proteins that control gene expression seemed to have an important role in coaxing α-cells to produce insulin in mice: Pdx1 and MafA.
Researchers at the University of Geneva first took islet cells from human pancreases, and separated out the individual cell types. They then introduced DNA that encoded Pdx1 and MafA proteins into the α-cells, before clumping them back together.
After one week in culture, almost 40% of the human α-cells were producing insulin, whereas control cells that hadn’t been reprogrammed were not. The reprogrammed cells also showed an increase in the expression of other genes related to β-cells. “They have a hybrid personality” said the researcher.
The team then implanted the mass of cells into diabetic mice, which had their β-cells destroyed, and found that blood-sugar levels went down to normal levels. When the cell grafts were removed, the mice’s blood sugar shot back up.
The researcher said that if α-cells or other kinds of islet cells could be made to start producing insulin in this way in people with diabetes, their quality of life might be greatly improved. The researchers hope to find a drug that can switch the identity of α-cells.
