Anti-Inflammatory Protein from the Liver Appears to Cure Type 1 in Mice

There are times when news from the labs produces a genuine hope that the war on diabetes has reached a significant turning point. This is one of those times.

| Oct 20, 2008

Diabetes Health has always been ambivalent when it comes to reporting diabetes research that involves mice. For one thing, although the critters are mammals, it's a stretch to say that what happens in a mouse can be duplicated in a human.

For another, research involving animals is only the first step in a long process. The laboratory breakthroughs so breathlessly hailed today may take five or ten years to work their way to trials with humans.

But despite those misgivings on our part, there are times when news from the labs produces a genuine hope that the war on diabetes has reached a significant turning point. This is one of those times.

Two teams of researchers have found that in mice with type 1 diabetes, a protein commonly used to treat pulmonary disease-related inflammation can restore insulin-producing beta cells and normal blood glucose levels. In some cases, the disease has been entirely cured. The protein, alpha1-antitrypsin (AAT), is produced in the liver and functions as an anti-inflammatory agent.

Previous theories about type 1 diabetes have proposed that inflammation is a result of the disease, not one of its causes. But the researchers, from the University of Colorado Health Science Center in Denver and Harvard Medical School in Cambridge, Massachusetts, knew from breakthrough research published in 2007 that inflammation and insulin resistance play a significant role in the onset of type 1.

Maria Koulmanda, PhD, an associate professor of surgery at Harvard Medical School, and her colleague, Terry Strom, MD, a professor of medicine at Harvard Medical School, hypothesized that inflammation triggers insulin resistance and faulty insulin signaling and is a primary instigator of T-cell attacks on pancreatic beta cells, which eventually destroys the ability of type 1 patients to produce their own insulin.

The teams also knew that AAT has been used for years to reduce inflammation in such respiratory conditions as chronic obstructive pulmonary disease and an inherited disorder that manifests much like emphysema.

They reasoned that by using AAT to lower the levels of muscle and fat inflammation in mice, they could restore insulin responsiveness and stop T-cells from mistakenly attacking pancreatic beta cells.

Results bore out their hopes. Administering AAT to non-obese diabetic mice not only lowered inflammation levels without interfering with T-cells' normal immune system tasks, but also restored insulin sensitivity, normal insulin signaling, and normal blood glucose concentrations.

The most striking result, said Koulmanda, was that the mass of still functioning beta cells in the mice expanded-something not seen before in research into type 1.

Great Implications for Transplants

The positive results from AAT amounted to a virtual cure for type 1- in mice. However, the implications for the use of AAT in humans are profound.

Typically, about half of transplanted cells are killed by inflammation within hours after being introduced into a patient's body, and the remainder die from inflammation within five years. In contrast, although the Colorado team treated their mice with AAT for only 14 days after transplanting beta cells into them, the cells survived and functioned for 120 days.

Thus, AAT may function as a "shield," protecting transplanted beta cells from inflammation long enough to allow them to thrive and reproduce. It is also possible that in patients with recently diagnosed type 1 who retain some functioning beta cells, AAT could similarly serve as a shield to prevent further beta cell loss.

AAT's effectiveness is something that researchers will want to test with human beta cell transplant recipients. Fortunately, AAT has been used in the medical community for more than 20 years, apparently with a good safety record. Researchers say that despite its powerful anti-inflammatory capabilities, the protein does not appear to interfere with the body's normal immune responses. This means that AAT may more quickly clear the regulatory hurdles in its path to use with human patients who have diabetes.

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Categories: Blood Glucose, Diabetes, Diabetes, Insulin, New Cure Research, Type 1 Issues

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Posted by Anonymous on 21 October 2008

There is an error of fact in one of Koulmanda's statements. He claims that a resurgence in beta cells has never been seen in type 1 research in mice before. This is not true. Dr. Denise Faustman of Mass General Hospital & Harvard Medical School cured type 1 diabetes in mice some years ago by killing the T-cells that were attacking the beta cells. The beta cells then were able to regenerate--without a transplant--curing the diabetes.

She is now in Phase 1 clinical trials using her treatment and preliminary results show that it's working as well in humans as it did in mice. Diabetes Health recently published a press release from Dr. Faustman announcing this promising result.

Posted by Anonymous on 24 October 2008

I read plenty about research triumphs and their results, etc., but all my doctor can do for me is prescribe insulin and testing supplies when not sick with some diabetes complication. I don't believe in anyone finding the cure...Because diabetes makes big profits to many out there. The moment the profits stop rolling in, the government(our taxes) will have to bail out.

Posted by Anonymous on 28 May 2009

Dear Anonymous,

I'm sorry to hear of your cynicism. The idea that no one is looking for a diabetes cure is absurd. The folks who sell insulin may be making profits off you and, sure, it would cut into their bottom line to cure you, but what about all the other companies out there? As a scientist in Biotech, I can assure you we would much prefer to impoverish them and provide you with a cure. Sadly, it so happens that diseases are hard to cure. Though thousands of scientists world-wide, both in the public and private sectors are working very very hard on diabetes it still might take awhile. This AAT advance is potentially huge because its already approved in humans. Now let's see how if it really works in people.

Posted by RebelTiger03 on 2 September 2009

Anti-Inflammatory Protein from the Liver Appears to Cure Type 1 in Mice

If this is so true. I want to contact person Who try this. Send me their email.
I want more infromation from the University of Colorado Health Science Center in Denver and Harvard Medical School in Cambridge, Massachusetts Where I can contact them about this.
Pls email me ASAP.


Posted by Anonymous on 7 December 2009

This news has been over a year and nothing really happened. If AAT has been showing its safety for over 20 years, what a big of deal of getting approval of clinical trial? Every researcher gets such big chunck of money from JDF or other fundation, only to publish a paper, get their tenure promotion, or become a full professor, nothing really done for saving real people's lives. There are many new findings each year, perhaps through those researches, you guys graduated many PhD students.... in reality, you guys did absolutely NOTHING to save human's life. Only to destroy a few rats. Bring on those research for real.

Posted by jrharris on 18 February 2010

The news over the recent years of this approach is, to say the least, exciting. Having been a Type I diabetic for 44 years (currently on a pump for the last 7), there's always a hope that there would be a 'cure' in my lifetime. This research appears to have promise. IF anyone has information relative to current trials either being planned, or being conducted, I'd be interested in hearing the details, and any applicable contact information. Thanks!

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