New Approach to Treating Type 1 Diabetes? Transforming Gut Cells Into Insulin Factories
Article can be found at: http://www.sciencedaily.com/releases/2012/03/120311150719.htm
A study by Columbia researchers suggests that cells in the patient's intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.
The research -- conducted in mice -- was published 11 March 2012 in the journal Nature Genetics.
Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.
A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.
The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili's lab.
The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.
Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisions -- Foxo1 -- the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood. "Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients," Dr. Accili says.
"Nobody would have predicted this result," Dr. Accili adds. "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 don't we get a cell that produces some other hormone? We don't yet know."
Insulin-producing cells in the gut would be hazardous if they did not release insulin in response to blood glucose levels. But the researchers say that the new intestinal cells have glucose-sensing receptors and do exactly that.
The insulin made by the gut cells also was released into the bloodstream, worked as well as normal insulin, and was made in sufficient quantity to nearly normalize blood glucose levels in otherwise diabetic mice.
"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 iPS stem cells," Dr. Accili says. The location of the cells in the gut may also prevent the diabetes from destroying the new insulin-producing cells, since the gastrointestinal tract is partly protected from attack by the immune system.
The key to turning the finding into a viable therapy, Dr. Accili says, will be to find a drug that has the same effect on the gastrointestinal progenitor cells in people as knocking out the Foxo1 gene does in mice. That should be possible, he says, since the researchers found that they could also create insulin-producing cells from progenitor cells by inhibiting Foxo1 with a chemical.
"It's important to realize that a new treatment for type I diabetes needs to be just as safe as, and more effective than, insulin," Dr. Accili says. "We can't 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."
The research was supported by the NIH (DK58282, DK64819, DK63608), the New York Stem Cell Foundation, and the Russell Berrie Foundation.
Replies to This Discussion
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Permalink Reply by gigem99 on
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Interesting. Thanks for the article. Once again, notably missing from the groups supporting the research is the JDRF. I guess they're too busy with the artificial pancreas. PFFT!
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Permalink Reply by Gary on -
I posted that over at Children with Diabetes forum a few days ago. I don't care much for the JDRF's choices of funding but they have been funding Viacyte who I believe has the best shot at this point to offer a breakthrough biological treatment in the US. The Artificial pancreas IMO is a waste. Not that it can't work but I think in the end to have a chance for it to function considerably better then we can do its going to require way too many gadgets. The most startling point of that article IMO is "Insulin is Safe"??? What planet on they on? Insulin is one of the most if not the most dangerous drugs in existence.
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Permalink Reply by MyBustedPancreas on -
Well, insulin isn't a drug - it's technically a biologic. Insulin is safe in the sense that you're simply replacing a hormone that your body should naturally be producing. It's dangerous because for many people, just a little too much can be deadly. I have an ISF of 50, so just one unit too much could kill me. Measure out a unit and see what a small difference this is. I did that not long ago and it really surprised me for some reason. (note: as a kid, diluting insulin wasn't uncommon and I don't know why there has been movement away from this practice, but I digress).
I actually agree with you regarding the artificial pancreas project. The more I read about it, the less I feel encouraged about it. First, it is really just another piece of technology that too many people won't be able to access because of cost. There are people here in the U.S. right now who don't have access to the basics that already exist - insulin, test strips, CGMs, pumps - because they simply can't afford them. And these are people WITH insurance.
A few years ago, I read something online about a young many with T1D who nearly died because he started a new job (with insurance) but there was a 6-month waiting period before the plan would cover his insulin and related supplies. He rationed his insulin and had lots of high BGs, but then ran out. He got really sick, went into DKA. This all happened over a period of just three months.
Why isn't there some assurance that type 1s will always have access to the basics to keep them alive?? Why isn't JDRF funding that??
I know insulin isn't a cure. I get that all too well. But I am alive and doing pretty darn well. While a cure would be nice, I can live like this, hopefully for a long time. Personally, I care more about the people who aren't able to afford the basics now. And I care more about what would happen should I lose my health insurance. How would I get what I need??
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Permalink Reply by smileandnod on -
Well said, MBP. My CDE told me of a gentleman that she saw who was rationing his insulin because he was in the Medicare donut-hole gap and couldn't afford more insulin. It's just wrong that we live in a country of such abundance and wealth and there are people who can't get the basics to stay alive. One of my biggest pet peeves.
I share your fear of losing your health insurance. My husband was laid off just recently for a few weeks and luckily our health insurance is through my employer. But it made me realize just how quickly it could be taken away. And then what?
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Permalink Reply by LadyD on -
I second that. Loss of insurance is always at the back of my mind. I was laid off once 8 years ago, fortunately my parents helped with the COBRA payments. They've since retired and I certainly don't want to burden them they've already done so much.
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Permalink Reply by smileandnod on
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I had the exact same response to the "Insulin is safe" comment. About as safe as a loaded gun. I wonder if the doctor quoted has ever used insulin himself... I would guess not.
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Permalink Reply by deanusa on -
really? so the alternative is better? not taking it? its not perfect because it is self administered. i dont understand why if a person thinks its so dangerous that that person would take it.the solution would be if a person really feels this way is not to take it.lol after 3 days someone might change their mind i think.
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Permalink Reply by smileandnod on
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An error of a little bit too much insulin could kill a person.... I don't equate that with "safe". A loaded gun is "safe" as long as you don't pull the trigger.
Of course I don't think the alternative is better and of course I take insulin to stay alive. I have what I believe to be a healthy respect and, yes, *fear* of insulin. I've experienced rapid and severe lows caused by taking insulin.
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Permalink Reply by deanusa on
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i get that. and many of us have had catastrophic lows.but there are many reasons why that happens.miscounting double dosing no reason at all complete screw up a monday or a full moon to much activity etc etc etc.insulin is not the scapegoat.lol im not sure of the number of people on insulin but if it was not safe im pretty sure that the resulting deaths could not be covered up.
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Permalink Reply by Gary on
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I would have died at least a dozen times over the last two years because of lows in my sleep had it not been for my elderly mom. While I am awake though I can on a rare occasion get down in the 30's I'm still able to help myself. Honestly without a cure I almost don't care if I die. This life is hell as far as I am concerned and how anyone with diabetes is actually OK with it is beyond my comprehension. Accepting it for me is not gonna happen.
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Permalink Reply by Harttj on
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I am sorry for anyone that feels life is not worth living because of being diabetic - there is so much more to life and living life even with diabetes. I hope anyone feeling that way will some day realize this.
I found a website that offers diabetic supplies at a good discount. Insulin is still expensive, but the rest of the supplies are cheaper than any other place I've seen - www.americandiabeteswholesale.com
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