GLOBAL. Type I diabetes has no cure. Currently Type I diabetics manage the disease with frequent finger pricks to test the glucose levels in their blood and injections of insulin corresponding to the results. These methods, while effective, are burdensome and painful. With 3 million Americans affected and 35 million worldwide, doctors and researchers are intent on improving treatment for the disease, and still hold out hope for a cure.
Looking to improve upon the status quo, Ryotaro Bouchi et al published a paper in Nature Communications on June 30th with promising results. The article states that turning off the FOXO1 gene has big implications. When this gene is inhibited in intestinal cells, they begin to produce insulin. What’s more, these cells are highly similar to pancreas beta cells that create insulin in a healthy endocrine system.
The researchers hope to apply this discovery in vivo in the coming years by targeting intestinal cells with a drug to inhibit FOXO1 gene expression. This drug would need to be taken continuously as the desired effect lasts one or two weeks at most – any longer and the immune system would begin to attack the insulin producers just as it did when the disease began. While medication could have side effects, it certainly seems preferable to daily finger sticks and injections.
This publication is sure to excite researchers and patients alike as it promises improvement in the daily life of Type I diabetics. To find out more information ROOSTERGNN turned to Dr. Domenico Accili, a Professor of Medicine at Columbia University and the Director for the Diabetes and Endocrinology Research Center there. He, along with Bouchi and a number of other co-authors, recently published the paper mentioned above. Accili agreed to a short phone interview to further discuss the elements of their research.
I see that you’ve been working on diabetes research for a long time but how did you get interested in this specific area?
Dr. Domenico Accili: It’s a long story but basically the key target of this study is one that we’ve been interested in for many years because of its many functions in metabolic control…the more recent observations were jump started about two years ago by a student in the lab who observed that when this gene is rendered inactive in the intestine some of the intestinal cells convert into insulin producing cells similar to those found in the pancreas.
Did the lab student come across this by accident?
We were looking at this gene because of its role in the pancreas proper and it turns out that the pancreas is very close to the intestine. Since we were analyzing the pancreas we also analyzed the intestine as a kind of negative control to make sure that nothing was amiss there. And on the whole we found these very bright insulin producing cells that were totally unexpected. In retrospect we could understand why this was happening and it didn’t look that surprising but still it was a serendipitous observation.
I’m wondering why you used iPS cells for the organoid?
We used iPS cells because we have an extensive iPS based operation here at the Diabetes Center at Columbia University. We’re hoping to develop [iPS cells] as a tool for cell transplantation but also (as demonstrated in our study) as a mechanism or tool to test new drugs or treatment. So the supply of iPS cells from our patients made it possible for us to engineer these gut organoids…what we wanted to do was essentially validate the mouse observations in human systems.
Do you think the iPS cells and the organoids you’ve created are similar enough that this same process could be replicated in vivo in humans?
In the study we go to great lengths to demonstrate how similar the gut organoids are to the human gut. I should say we did not discover how to make gut organoids: this was discovered by a very bright fellow at the University of Cincinnati by the name of James Wells. The system of making gut organoids is now well established in the community and it really looks very similar to the intestine. Based on that we had great hopes that once we had a drug that could complete the same feat we accomplished in the test tube that it would work also in the human gut.
What do you plan on doing next?
So I can tell you what we’re doing right now and that is to make a drug that can be given to the people that will do exactly what we saw in the organoid culture. We’re trying to make an inhibitor of the gene that we inhibited in vitro and we’re trying to find a formulation that is safe and effective to give to people so that we can do a clinical trial with it. It’s still, I would say, a couple of years away, before we have a compound that we feel safe testing in humans but that’s the direction we’re headed toward.
While the drug may be a few years down the line, this discovery is certainly exciting. The less invasive treatment for type I diabetes, and the self-sufficient production of insulin would be a distinct improvement in disease management. The work Bouchi, Accili and their team is doing promises great results in the coming years.