Is the Induction of Insulin Production in Gut Stem Cells a Possible Treatment for Diabetes?

Abolishing the activity of the Foxo1 gene in mouse gut Neurog3+ progenitor cells caused these cells to differentiate into a type capable of producing fully active insulin.

Stem cell therapy to replace insulin producing pancreatic beta cells has been considered for treatment of type I diabetes. However, such cells would not be under hormonal control and could produce dangerously high levels of insulin.

Another approach is to induce other types of normally occurring cells to manufacture the hormone. Investigators at Columbia University (New York, NY, USA) inadvertently revealed the potential of this technique when they used genetic engineering to abolish the activity of the mouse Foxo1gene in gut stem cells known as Neurog3+ progenitor cells.

The investigators reported in the March 11, 2012, issue of the journal Nature Genetics that Neurog3+ progenitors actually require active Foxo1 to prevent differentiation into insulin producing cells. Without Foxo1 the gut cells produced insulin that was released into the bloodstream where it worked as well as normal insulin. The gut cells produced insulin in sufficient quantity to nearly normalize 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,” said senior author Dr. Domenico Accili, professor of medicine at Columbia University. “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 do we not get a cell that produces some other hormone? We do not yet know.”

“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 or induced pluripotent stem cells,” said Dr. Accili. “However, it is important to realize that a new treatment for type I diabetes needs to be just as safe as, and more effective than, insulin. We cannot 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.”

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