Researchers Take New Approach to Treating Type 1 Diabetes

Columbia researchers have some promising new results based on a recent diabetes clinical study. According to their study, it might be possible to coax cells in the patient’s intestine into producing insulin! Successfully doing this would mean that the patient would no longer need to undergo a stem cell transplant. Up until now, most researchers believed that a stem cell transplant was the ideal way to replace the cells lost in type 1 diabetes, which allows patients to stop taking insulin injections. The Columbia researchers had conducted this recent trial with mice, and their results were published in the March 2012 edition of Nature Genetics.

As you may already be aware, type 1 diabetes is an autoimmune disease which destroys the insulin producing cells in the patient’s pancreas. The pancreas does not have the ability to replace the lost cells, so a patient with type 1 diabetes needs to inject themselves with insulin in order to keep their blood glucose levels in check. If these blood glucose levels are not kept in check, it can be life threatening to the T1D patient. In order to maintain healthy blood glucose levels, patients should monitor their levels several times a day.

(See also: Symptoms of Type I Diabetes)

For a while now, researchers have been trying to develop an effective method of replacing these lost cells in the pancreas with new cells which can release insulin into the patient’s bloodstream when required. At this point, we are able to create insulin-producing cells in a laboratory setting utilizing embryonic stem cells. However, these manufactured cells are not yet ready for transplantation, because they do not yet release adequate amounts of insulin in response to the patient’s blood glucose levels. Basically, the patient would receive insulin when it’s not needed, which could lead to hypoglycemia (this can be fatal!).

Dr. Domenico Accili, a professor of medicine at Columbia University Medical Center, and Dr. Chutima Talchai conducted this recent diabetes clinical trial. The results have shown that particular progenitor cells located in the intestine of mice actually have the ability to make insulin-producing cells. Dr. Talchai also works as a postdoctoral fellow for Dr. Accili’s in her lab.

Normally, these gastrointestinal progenitor cells are responsible for creating a wide range of other cells. Among these are cells that produce gastric inhibitory peptide, serotonin, and a variety of other hormones which then get secreted into the subject’s GI tract and bloodstream.
During the study, the doctors found that when they turned off the Foxo1, a gene which plays an important role in cell fate decisions, the subject’s progenitor cells would generate insulin producing cells. When they switched off Foxo1 at an earlier stage, even more cells were generated.

However, the insulin producing cells were still be generated when Foxo1 was turned off after the mice had been fully developed. According to Dr. Accili, these results show that it could be possible to regrow insulin producing cells in gastrointestinal tracts of children and adults who have been diagnosed with type 1 diabetes.

Dr. Accili would be the first to tell you that this discovery was unexpected. There were a number of different things that could have happened after they switched off Foxo1. Interestingly, when Foxo1 is turned off in the pancreas, nothing happens. This begs the question, “What makes the gut so special?” As of now, this remains a question with no clear answer.

Incredibly, the insulin-producing cells located in the gut would actually be harmful, if it were not for the fact that they release insulin in response to the subject’s blood glucose levels. As the researchers point out, these new intestinal cells possess glucose-sensing receptors which allow them to get a measure of the blood glucose levels.

Even more astonishing, the insulin that is produced by these gut cells is just as effective as normal insulin, and enough of it gets produced to bring the subject’s blood glucose to nearly normal levels. Plus, the insulin gets released by the gut cells into the subject’s bloodstream.
Compared to the previous therapies based on iPS or embryonic stem cells, these results show that manipulating a patient’s gut into making these insulin-producing cells would be a more effective way of treating diabetes. Dr. Accili has also noted that the location of the new insulin-producing cells could keep them from being destroyed by the diabetes, because our GI tract is partially protected from any attacks from our immune system.

The next step for researchers will be developing a drug which can provide the same effect on the gastrointestinal progenitor cells in human subjects as knocking out the Foxo1 gene has in mice. Dr. Accili is confident that this will be possible, since they discovered it was possible to use a chemical to inhibit the Foxo1 gene and cause the progenitor cells to create the insulin-producing cells. In the end, the key will be developing a treatment which is not only more effective than the insulin injections, but also just as safe.

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