Type 1 diabetes is caused by the body’s immune system attacking its own natural insulin producing cells to the point where the body cannot properly regulate blood sugar levels. Researchers have been pursuing therapies that could retrain the body’s other cells to produce the proper amount of insulin.
According to a new report in Nature Communications, by switching off a single gene, scientists at Columbia University’s Naomi Berrie Diabetes Center have converted human gastrointestinal cells into insulin producing cells, demonstrating in principle that a drug could retrain cells inside a person’s GI tract to produce insulin.
“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,” said study author Dr. Domenico Accili, a medical professor at Columbia University Medical Center (CUMC).
The study team said their finding opens the door to the possibility of treating or curing type 1 diabetes through the reprogramming of existing cells rather than through transplants or stem cells. Although insulin-producing tissue can be produced in the lab from stem cells, these cells do not yet possess all the capabilities of natural pancreatic beta cells.
The method, described today in the journal Nature Communications, raises the possibility of replacing insulin making pancreatic beta cells lost in diabetics by using a drug to retrain patients’ existing cells.
“While progress has been made in generating beta cells from stem cells, the method hasn’t yet produced ones with all the needed functions,” said Domenico Accili, the study’s lead author. Plus, such cells would require transplantation.
However, by simply turning off a particular gene, the Columbia scientists were able to convert cells in the human gut into cells that make insulin. They said the findings suggest that reeducating existing cells may be an easier way to replace the cells lost in type 1 diabetes than creating new cells using stem cell technology.
For nearly two decades researchers have been trying to make surrogate insulin producing cells for type 1 diabetes patients. In type 1 diabetes, the body’s natural insulin producing cells are destroyed by the immune system.
Although insulin-producing cells can now be made in the lab from stem cells, these cells do not yet have all the functions of naturally occurring pancreatic beta cells.
This has led some researchers to try instead to transform existing cells in a patient into insulin-producers. Previous work by Dr. Accili’s lab had shown that mouse intestinal cells can be transformed into insulin-producing cells; the current Columbia study shows that this technique also works in human cells.
The Columbia researchers were able to teach human gut cells to make insulin in response to physiological circumstances by deactivating the cells’ FOXO1 gene.
The team’s earlier work with mouse intestinal cells showed that reeducation could lead to healthy blood glucose levels in otherwise diabetic mice.
“Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients,” Accili said at the time.
“Nobody would have predicted this result,” Accili added. “Many things could have happened after we knocked out Foxo1. In the pancreas, when we knock out Foxo1, nothing happens. So why does something happen in the gut? Why don’t we get a cell that produces some other hormone? We don’t yet know.”