The Regeneration of Beta Cells

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I was diagnosed with type 1 diabetes nearly 16 months ago.  At the time of my diagnosis I was horrified, but also a little bit cocky.  My husband has had type 1 diabetes  since 2002 and after over six years of living with a diabetic, I was sure I knew all I needed to know about managing diabetes.  I thought I’d breeze my way into life as a diabetic – and then I had my first hypoglycemic attack, a sort of rite of passage.

What I quickly learned was that no matter how much information you have and no matter how close you’ve been to a diabetic, you don’t really know diabetes until it’s in your blood.  And so while I still maintain to know an inordinate amount of information about my pancreas, I don’t claim to know it all.  Not even close.   In fact, new research on the defunct organ poking from beneath my stomach like a hitchhiker’s thumb indicates pancreatic cells are capable of something I’d never imagined – regeneration.  A study, conducted at the University of Geneva and co-funded by the Juvenile Diabetes Research Foundation,  has found that alpha cells in the pancreas, the cells which secrete the hormone glucagon, can regenerate themselves into insulin-producing beta cells after normal beta cells have been destroyed.  The study is the first to show that this change of alpha cell into beta cell can happen naturally and spontaneously.

The researchers, led by Dr. Pedro L. Herrera, discovered that when they destroyed beta cells in mice to induce an artificial form of type 1 diabetes, the alpha cells in the pancreas  then changed into insulin-producers.  They found that when nearly all of the beta cells had been destroyed, if mice were given insulin therapy to keep them alive, the alpha cells spontaneously changed into functioning beta cells. After enough alpha cells converted into beta cells, insulin therapy was no longer needed.  The Geneva researchers pointed out that the critical factor in sparking the alpha-to- beta-cell reprogramming was removing (or ablating) nearly all the original insulin-producing cells in the mice. In mice where the loss of beta cells was more modest, the researchers either found no evidence of beta cell regeneration (when only half the cells were destroyed) or less alpha cell reprogramming (when less than 95% of cells were destroyed).

While I’m aware that this is research in its infancy and far from a cure,  reading about a study which includes the words “insulin therapy no longer needed” brings to mind Moses seeing the Promised Land.  The catch, however, is that type 1 diabetes is an autoimmune disease in which the body kills off its own beta cells, and chances are that the immune system would destroy any newly regenerated beta cells, just as it destroyed the original cells.  Nonetheless, the research is promising and this study is another step forward for JDRF’s research focus on Regeneration as a potential pathway to restore insulin production – and normal blood sugar in people with type 1 diabetes.  I had the opportunity to send some questions to Dr. Andrew Rakeman, JDRF Program Manager in Beta Cell Therapies, to learn more about the study.

Is this the first time alpha cells are being considered as a potential source of cells for beta cell treatment in diabetics?

It has been previously shown that alpha cells can be converted into beta cells, but this work relied on genetic manipulations – forcing expression of a key beta cell transcription factor, Pax4, in alpha cells. What is new in Dr. Herrera’s work is the demonstration that the ability of alpha cells to convert to beta cells appears to be intrinsic and can occur without genetic manipulation of the cells.  We know a bit about some of the transcriptional changes that accompany the conversion of alpha cells to beta cells, but we still do not know the signals that trigger those changes. One of the current challenges is to identify the signals and pathways that are triggering the reprogramming of alpha cells to beta cells and ways to manipulate those pathways.

Are efforts being made to convert alpha cells to beta cells in vitro to see if we can increase the supply of beta cells for transplantation?

The first likely application for any beta cell reprogramming effort would be in vitro reprogramming for transplantation. However, when considering alpha cells as a starting cell it is important to remember that beta cells outnumber alpha cells in human islets. Therefore even a perfect conversion of all alpha cells would only give a modest increase in the number of beta cells available for transplant.

Many different studies have shown that we can make insulin producing cells. Do you believe that this is different and if so, how?

Being a beta cell is more than just producing insulin. Beta cells must be able to continuously sense the level of glucose and secrete insulin appropriately in response to the body’s needs. What is exciting about these results is the demonstration that the body can spontaneously make new beta cells from pre-existing alpha cells and that these new beta cells are functional and able to control glucose levels. The demonstration that the conversion of alpha cells to beta cells is a spontaneous and normal process raises hope that we can identify therapeutic interventions that will mimic this process to safely and efficiently reprogram alpha cells to beta cells for the treatment of diabetes.

There is research that shows the cells that line the ducts of the pancreas can convert to beta cells.  Do you think these findings contradict or support the idea that beta cells might come from ducts?

These findings don’t rule out a ductal or duct-associated beta cell progenitor. One of the emerging themes coming from this work and other work is that the pancreas is more plastic than we previously appreciated – there appear to be multiple mechanisms and sources for beta cell regeneration.

Do you think these findings will significantly change the focus of research on the search for the beta cell stem cell?

JDRF maintains an active interest in identifying and characterizing an adult beta cell stem cell and will continue to support research in this regard. These and other recent results have increased our interest and support of research aimed at reprogramming of non-beta cells to beta cells. Reprogramming is emerging as a new priority area and growing part of our portfolio.

Do you dream about a clinical application for this?

At JDRF we are hopeful that reprogramming will one day become a clinical reality. However, it is important to remember that we are at very early stages – we still need to gain better insights into the pathways and triggers that tell alpha cells to convert to beta cells and develop strategies and approaches to manipulate those pathways.

For more details see Karmel Allison’s post.

Jessica Apple is co-founder and editor-in-chief of ASweetLife.  She writes the blog The Natural Diabetic.

Comments (8)

  1. A little shocked at

    Not to be a jerk or paranoid, but what did the doctors say about a wife getting Type 1 when her husband has had it for six years?
    There must be something to this?

  2. Scott S at

    I am somewhat troubled by all of the press that this news story has garnered, in part, because #1) this is yet another mouse trial, but it’s worth noting that at present, there are close to 2 dozen cures that have worked in mice, yet none have translated successfully into success in human patients #2) equally important, the mice in this trial were NOT spontaneously autoimmune, meaning these mice were given chemicals that destroyed their pancreatic beta cells, they did not develop autoimmune diabetes naturally, raising questions on the applicability to even the NOD mouse model, let alone patients with type 1 diabetes and #3) finally, another concern is the suggestion that all scientists would need to do is convert some alpha cells into insulin-producing beta cells, solve the autoimmunity puzzle and voila, they’d be cured.   You have already noted that the ratio of beta cells to alpha cells is already large, so there aren’t enough beta cells to convert in the first place.  Another factor to consider is that in people with type 1 diabetes, the autoimmune inflammation that causes the disease also permanently damages the remaining beta cells (the immune system attacks the islets which contain alpha, beta and delta cells — the beta cells are the target, but all of the other cells in the islets are damaged in the process) which renders most patients with type 1 diabetes without even fully-functional counterregulatory function to protect them from hypoglycemia.  If the few remaining alpha cells are dysfunctional, what makes scientists believe these can easily be converted into fully-functional beta cells?
    While this news is interesting, it likely received more press than it legitimately deserves at this early point in time.

  3. Tianshi at

    As the key working in the pancreas ,it will be revolutionary for the disease

  4. Lance at

    Here’s some advice:  take a week to gradually reduce your caffeine intake to zero, then don’t consume caffeine. No coffee, tea, soda or anything that has caffeine. Caffeine, once consumed, produces alloxan (related to uric acid) which is toxic to your insulin-producing Beta cells in the pancreas. (Additionally, stay away from Decaf coffee and tea because they contain some harmful caffeine-related compounds that are not good for Beta cells.)

    As long as you stay clear of the toxicity of caffeine, your Beta cells may very well regenerate and eventually let you get off diabetic meds and insulin.

    Good luck to you!

  5. Richard at

    Ultraviolet Blood Therapy (UBT), a simple OP procedure, stops autoimmune attacks by “resetting” the immune system.  Since Beta cells are been constantly produced from alpha cells by the body only to be destroyed by continues autoimmune attacks, UBT should cure type 1 diabetes.

  6. anna at

    In 1987 we were told this same information when our daughter at age two and a half was diagnosed with type one diabetes.  Now, her daughter also has diabetes.  I believe there has been a cure and drug companies would go bankrupt if it were known. I cling to HOPE that one day these two ladies we love so much will not have to live with this dreadful disease.

  7. As of today, August 05, 2011 – what company is currently pursuing an FDA approval for a functional method of ‘beta cell regeneration’? Who are the viable contenders?
     
    Thanks for your feedback!

  8. Richard at

    Further to by 4/25/11 comment above: You can learn about UBT by going to DrsUBI.com.  UBT is known to moderste the auto-immune response in cases such as Lupus – another auto-immune disease.  UBT has been used successfully for 75 years – but in the 1950s, Morris Fishbein at JAMA and AMA drove it underground to protect the anti-biotic industry.  There are no serious side-effects.  UBT is flourishing in Europe and the are about 300 Integrative doctors using it in the US.

    Could it be that the success of islet transplants is the immuno-suppressive drugs given to prevent rejection rather than the transplanted cells themselves.  By suppressing the continuous auto-immune attacks on the beta cells produced naturally by alpha cells, the beta cells can develop to the point where they generate enough insulin and the patient will be cured of their Type 1 Diabetes.

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