Getting Insulin from Gut Cells: Diabetes Cure Research


Gut Cells

Imagine millions of tiny insulin pumps that work really well, measuring your blood sugar hundreds of times each second and secreting just the right amount of insulin.  That’s basically how the beta cells of a healthy individual’s pancreas work. Ben Stanger, M.D., Ph.D., and his research team at the University of Pennsylvania believe that people with Type 1 diabetes could harbor similar cells in their gut, and that these cells could work much better than any current form of insulin or drug therapy.

The introduction of beta-like cells into a patient to treat diabetes is a form of cell therapy. Dr. Stanger’s lab uses an approach called cellular reprogramming, which he delights in calling “cellular alchemy,” to transform cells on a genetic level. He has shown that gut cells in mice can be manipulated to detect and stabilize blood glucose levels, just like healthy beta cells. Dr. Stanger has conducted experiments on mice and samples of human intestinal cells grown in a lab, and he hopes to begin clinical studies on human subjects in the next five to 10 years.

Insulin therapy, whether by injections or a pump, is designed to mimic a functional pancreas. But doctors and patients alike recognize, even the most sophisticated pump and diligent patient can’t regulate blood glucose levels on par with an army of healthy beta cells.

“If we really want to have an effective therapy for diabetes, we need something that works as well as a beta cell,” Dr. Stanger explains, adding that cell therapy, rather than insulin or drug therapy, “actually gives cells back to people to replace the ones that are no longer working or have been destroyed.”

Efforts to treat diabetes using cell therapy have been underway for decades. From 2000-2010, most research focused on the development of embryonic stem cells that behave like beta cells. But embryonic stem cell research has been hindered by ethical and political controversy, as well as scientific limitations. Among other challenges, the body will naturally reject embryonic stem cells from a donor, considering them potentially dangerous intruders. Immunosuppressants can help the transplanted cells survive, but the patient is then at risk for various side effects, including increased susceptibility to infections. Finally, the supply of egg donors for stem cell research is limited.

By using gut cells from the patient instead of an embryonic stem cell from an external donor, Dr. Stanger aims to circumvent all of these issues.

The Edmonton Protocol: Thinking Beyond the Pancreas

How is it that a cell can do the job of a beta cell while sitting in the intestine? If the pancreas is blood sugar headquarters, is it possible for a group of volunteer beta-like cells to work remotely?

It turns out that it’s very possible indeed, which opens up all sorts of cell therapy possibilities, in the intestines and beyond. This became apparent following research out of the University of Alberta in Edmonton, published in the New England Journal of Medicine in 2000. In this study, now known as the Edmonton protocol, patients with Type 1 diabetes received pancreatic islet transplants into the portal vein, and subsequently maintained healthy blood sugar levels without insulin therapy. Those successes, however, did not last; after several years, all patients once again returned to their previous dependence on insulin.

While the Edmonton protocol did not bring about lasting blood glucose control, it showed that beta-like cells could function (albeit with varying success) outside of the pancreas, so long as they are in direct contact with blood. This direct contact enables cells to detect blood glucose levels and secrete the appropriate amount of insulin, whether they reside in the pancreas, liver, gut, or elsewhere. Just like millions of high-performing tiny insulin pumps.

Which brings us back to the gut. As Dr. Stanger’s research progresses, he hopes to develop beta-like gut cells that are even more like beta cells than those in his petri dishes and mice today – even more responsive and capable of regulating blood glucose levels from the intestine.

Can This Work for People With Type 1 Diabetes?

 Dr. Stanger’s research focuses on developing cells that would support people with Type 1 diabetes, a population with an autoimmune response that destroys beta cells. So the question is, will these faux beta cells be destroyed in the same fell swoop?

While that crucial question has not been conclusively answered, Dr. Stanger is optimistic. The prevailing opinion is that in the Edmonton protocol, the expiration of the transplanted pancreatic islets was not due to an autoimmune response. (Islets fail for a variety of reasons, but that immune attack does not seem to be the principal one.) So it is plausible that the beta-like gut cells in Dr. Stanger’s lab will be “different enough” that they won’t trigger an autoimmune response.

It’s important to note, however, that despite Dr. Stanger’s promising research, and that of others, including Timothy Kieffer at the University of British Columbia, who are working on similar approaches, we are still a long way from making real, human-usable beta cells from gut cells.

If you are hopeful that this research will translate into an applicable treatment for Type 1 diabetes, you can help by urging your representatives in Congress to support National Institute of Health funding, as well as by getting involved with organizations that support diabetes research such as the JDRF and American Diabetes Association.

*Image published in Cell Reports – Courtesy Yi-Ju Chen and Ben Stanger

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Kathy White
9 years ago

I’m excited to see this study.  I am an islet cell recipient and have learned first hand how having functioning islets again can transform your health and well being.  They lasted almost 5 years and even as they were weakening, my blood sugars were very easily controlled.  

Any method of getting islets should be supported and applauded.  We have the resources to make this happen, we only need to support these brilliant and dedicated researchers to make it our reality. 

9 years ago

Get signed up with the Juvenile Diabetes Cure Alliance. They are on the right track. The hundreds of millions of dollars fundraised or lobbied out of the pockets of governments are being spent in a diffuse, desultory way. The JDCA seeks to hold JDRF, ADA and other major research foundation’s feet to the fire to make sure they stay focussed on the task at hand — finding a cure urgently. Neither complaining nor holding blind faith in the medical research industry will relieve people of the burden of diabetes in the near future. Add your voice to JDCA’s efforts to… Read more »

9 years ago

There will be no cure no time soon….there is too much money in treatments not cures….sickness is a multi-billion dollar industry and the corporations want to continue making money….also they believe that cures will affect the economy imagine all the organizations, foundations, walks for cures, special disease institutions, specialists, medical equipment etc. not necessary anymore there would be a lot of people out of work and the corps don’t want that so…..the people in power will have to change their hearts and create alternative jobs in order to cure diseases. So sad for our love ones who suffer.

Jessica Apple
9 years ago

I get frustrated by comments like the ones above.  The human body is complicated!  I don’t like false promises either, but complaining isn’t going to bring a cure.  Participate in TrialNet  Fundraise for research.  Encourage the NIH to spend more on type 1.  Lots we can do to try to push research forward.  

Bill Marsh
Bill Marsh
9 years ago

I have to agree with the sentiment of the first comment.  Five to ten years to do clinical human studies?!?!  Maybe Apple, Samsung, Tesla or some other tech companies should get into medical research.  Tech companies apparently understand how to accelerate scientific and technical innovations.  The glacial pace of diabetes research (which I have been closely following for over 30 years) appears to be accepted as the status quo by the medical research establishment.  Time does not appear to be a factor in this area of medical research, while millions of lives are destroyed throughout the globe.  The research-to-implementation processes… Read more »

9 years ago

blah blah blah just 5 to 10 years away blah blah blah

I propose we rename Type 1 to Type 5 to 10 because any possible cure is just 5 to 10 years down the road..

Please, enough already.  It didn’t take this long to send a man to the moon. 

9 years ago

blah blah blah 5 to 10 years blah blah blah

Maybe we should just renamy type 1 to Type 5 to 10 because any possible cure is just 5 to 10 years down the road.  

Please, enough already.. 

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