By switching off one single gene, researchers have turned human gastrointestinal cells into insulin producers. Retraining GI cells this way could help replace insulin-producing cells that are destroyed because of diabetes.
“People have been talking about turning one cell into another for a long time, but until now we hadn’t gotten to the point of creating a fully functional insulin-producing cell by the manipulation of a single target,” Columbia University’s Domenico Accili explains in a press release.
In type I diabetes, the immune system attacks the body’s insulin-producing cells in the pancreas, and over time, sugars build up in the blood. And while surrogate cells have been developed in the lab using stem cells, the resulting cells don’t have all the functions of naturally occurring pancreatic beta cells.
In work published in 2012, Accili and colleagues described a method of converting mouse gut cells into insulin-producing ones. Once released into the bloodstream, insulin made this way worked like normal insulin, regulating blood glucose levels in diabetic mice.
Now, the team shows that the technique works in human intestinal cells too. In a miniature tissue model of the intestine -- which they created using human pluripotent stem cells -- the team deactivated the gut cells’ FOXO1 gene, which is tied to metabolic regulation. After a week, the cells started releasing insulin in response to glucose.
The team is currently looking for compounds that would inhibit FOXO1 in the gastrointestinal cells of people and expects clinical trials to start in a year or two.
The work was published in Nature Communications this week.