The study was carried out by Chutima Talchai, Ph.D, a New York Stem Cell Foundation-Druckenmiller Fellow, and Domenico Accili, M.D., professor of medicine at Columbia University Medical Center.
Type 1 diabetes is an autoimmune disease that kills cells in the pancreas which produce insulin, resulting in high levels of glucose in the blood. As the pancreas is unable to replace these cells, individuals suffering with the disease must inject insulin into themselves in order to manage their blood sugar. Patients must also monitor their sugar levels numerous times a day, as blood glucose that is too low or too high can be fatal.
For scientists researching type 1 diabetes, one of the leading goals is to replace lost insulin-producing cells with new cells that release insulin into the bloodstream as needed. Even though researchers are able to generate these cells in the laboratory from embryonic stem cells, they are not suitable for transplant in patients as they do not release insulin appropriately in response to sugar levels, potentially resulting in a deadly condition called hypoglycemia.
In the intestine of mice, the researchers found that certain gastrointestinal progenitor cells are able to generate insulin-producing cells.
Usually, progenitor cells are responsible for generating a vast range of cells, such as gastric inhibitory peptide, cells that produce serotonin, as well as other hormones secreted into the GI tract and bloodstream.
The researchers discovered that when they switched off Foxo1 (a gene known to contribute in cell fate decisions), the progenitor cells also generated cells that produced insulin. In addition, the team found that although more cells were produced when Foxo1 was switched off early in development, they were also produced when the Foxo1 was switched off in adult mice.
Dr. Accili, explained:
"Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients.
Nobody would have predicted this result. 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."
If insulin-producing cells in the gut did not release insulin in response to blood sugar levels they would be dangerous. However, according to the researchers, the new intestinal cells are able to release insulin in response to sugar levels as they have glucose-sensing receptors.
In addition, the researchers found that the insulin produced by the intestinal cells was made in enough quantity to almost normalize blood sugar levels in otherwise diabetic mice, was released into the bloodstream, and worked the same as normal insulin.
Dr. Accili, said:
"All these findings make us think that coaxing a patient's gut to make insulin-producing cells would be a better way to treat diabetes than therapies based on embryonic of iPS stem cells."
Furthermore, as the gastrointestinal tract is partly protected from attack by the immune system, the location of the intestinal cells may block the diabetes from killing the new insulin-producing cells.
According to Dr. Accili, in order to turn the finding into a suitable therapy a medication will need to be found that produces the same effect on the progenitor cells in individuals as switching off the Foxo1 gene does in mice. Accili explains that this should be possible as they discovered that they could produce insulin-producing cells from progenitor cells by preventing Foxo1 with a chemical.
Dr. Accili, explained:
"It's important to realize that a new treatment for type 1 diabetes needs to just as safe as, and more effective than, insulin. We can't test treatments that are risky just to remove the burden of daily injections. Insulin is not simple or perfect, but it works and it is safe."
The study received funding from the NIH (DK58282, DK64819, DK63608), the New York Stem Cell Foundation, and the Russell Berrie Foundation.
The researchers report no financial or other conflict of interest.
Additional contributors are Shouhong Xuan (CUMC), Tadahiro Kitamura (Gunma University, Maebashi, Japan), and Ronald A DePinho (Harvard Medical School).