Posted on 08/11/2012 3:20:17 PM PDT by neverdem
At its most fundamental level, diabetes is a disease characterized by stress -- microscopic stress that causes inflammation and the loss of insulin production in the pancreas, and system-wide stress due to the loss of that blood-sugar-regulating hormone.
Now, researchers led by scientists at the University of California, San Francisco (UCSF) have uncovered a new key player in amplifying this stress in the earliest stages of diabetes: a molecule called thioredoxin-interacting protein (TXNIP). The molecule, they've discovered, is central to the inflammatory process that leads to the death of the cells in the human pancreas that produce insulin.
"This molecule does something remarkable -- it takes stress and makes it worse," said the senior author of the study, UCSF's Feroz Papa, MD, PhD, an associate professor of medicine at UCSF and a member of the UCSF Diabetes Center and the California Institute for Quantitative Biosciences (QB3).
The study is published this week in the journal Cell Metabolism, with a parallel study by researchers at Washington University in St. Louis. Both studies were funded by the Juvenile Diabetes Research Foundation (JDRF).
The work provides a roadmap for finding new drugs that could target and shut down the action of TXNIP, thus preventing or stalling the inflammatory processes it amplifies. Researchers in the field believe that this strategy could benefit people in the early days of the disease, when diabetes is first developing or is soon to develop -- a time referred to as the "honeymoon" period.
Clinical studies have already shown that dietary changes and other approaches can extend the honeymoon period in some people and prevent diabetes in others. The overarching goal of Papa's research, he said, is to find a way to extend this honeymoon period indefinitely.
Diabetes and the Loss of Beta Cells
Diabetes is a major health concern in the United States, affecting an estimated 8.3 percent of the U.S. population -- some 25.8 million Americans -- and costing U.S. taxpayers more than $200 billion annually. In California alone, an estimated 4 million people (one out of every seven adults) has type 2 diabetes, and millions more are at risk of developing it. These numbers are poised to explode in the next half century if more is not done to prevent the disease.
At the heart of diabetes is the specialized hormone-producing beta cells, which dot the human pancreas and produce the insulin that helps regulate a person's blood sugar.
These beta cells are like tiny biological factories that churn out insulin. A single beta cell might make a million molecules of insulin a minute. That means the billion or so beta cells in the average healthy pancreas will make more copies of insulin every year than there are grains of sand on every beach and in every desert in the world.
They are part of a delicate balance, however, and if the beta cells are lost, the pancreas may not be able to produce enough insulin and the body may not be able maintain proper blood sugar levels. That's exactly what happens in diabetes.
Stress to the Cells
Papa and his colleagues have found in recent years that underlying beta cell destruction and diabetes is stress within a part of the cell known as the endoplasmic reticulum (ER).
All cells have these structures, and the enveloped folds of the ER are easily spotted under a microscope. They play a crucial role in all human cells by helping to process and fold proteins the cells produce. But for beta cells, this structure is critical to their specialized function of secreting insulin.
If one thinks of a beta cell as a little factory, the ER would be like the shipping warehouse -- the packaging place where the end products are nicely wrapped, tagged with address labels, and sent to their final destination.
A healthy ER is like a well-run warehouse. Items are processed, packaged and shipped efficiently. A stressed ER, however, resembles a warehouse in shambles, with unboxed cargo accumulating everywhere. The longer this continues, the worse it becomes, and the body's solution to the problem is somewhat drastic: it essentially burns the factory down and closes the warehouse.
In scientific terms, the cell initiates what is known as the "unfolded protein response" in the ER, which activates inflammation through a protein known as interleukin-1 (IL-1). This process ultimately leads to apoptosis, the self-implosion of the beta cell.
For a whole organism, this is not as drastic as it sounds—with a billion or more beta cells in the pancreas, most people can afford to lose a few. The problem is that for far too many people, there are far too many warehouses burning down.
"There's not a lot of reserve in the human pancreas -- if these cells start dying, the remaining cells have to work harder," Papa said. Past some tipping point, the balance is lost and diabetes develops.
The Discovery of TXNIP's Role
Recognizing the importance of the inflammatory process in the development of diabetes, several pharmaceutical companies already have clinical trials underway to test potential new drugs that target the IL-1 protein.
In the new work, the UCSF team highlighted the protein TXNIP as a potential new target, until now an underappreciated central player in this process. TXNIP is involved in initiation of this destructive process of ER stress, unfolded protein response, inflammation and cell death.
They found that, as this process begins, a protein called IRE1 induces TXNIP, which leads directly to IL-1 production and inflammation. Removing TXNIP from the equation protects cells from death. In fact, when mice without this protein are bred with mice prone to developing diabetes, the offspring are completely protected against the disease because their insulin-producing beta cells survive.
What this suggests, said Papa, is that inhibiting TXNIP in people may protect their beta cells, perhaps delaying the onset of diabetes -- an idea that that will now have to be developed, translated and tested in clinical trials. Source : University of California - San Francisco
Innate immunity: Review on the activation of the inflammasome...
Additional interesting info:
BCG Vaccine May Reverse Type 1 Diabetes
http://www.freerepublic.com/focus/f-news/2917334/posts
Like, *PING*, dudes and dude-ettes.
Type one diabetes is an autoimmune disease where hepcidin is secreted (from the iron loaded liver)that blocks the beta cells from excreting iron through ferroportin receptors. The beta cells eventually become iron loaded and the object of attack from the killer T cells. Insulin production drops(as intended) as the beta cells are obliterated by the killer T cells. If the insulin production stays high the iron loaded liver and pancreas become more iron loaded and more at risk to cancer. The solution to this puzzle is to down load iron from the pancreas and the liver.
I have diabetes and use cinnamon, nettle powder and ginger. I eat healthy, always have. But these spices have made it so I need no insulin or drugs like Glyburide. That stuff made me feel like sh!t.
No shaking and no up and down on my sugar levels.
Teaspoon of each one everyday. Takes about two weeks to settle into your system and you must eat healthy. No Oreos, ice cream or potato chips.
Ping.
FReepmail me if you want on or off my combined microbiology/immunology and/or separate diabetes ping lists. The connection here is inflammation and the innate immune system.
That is so great.. I totally believe in the power of herbs and supplements (alternative medicine).
Turmeric is also good for inflammation and has been shown to battle melanoma pretty well in studies on animals.
That is so great.. I totally believe in the power of herbs and supplements (alternative medicine).
Turmeric is also good for inflammation and has been shown to battle melanoma pretty well in studies on animals.
There is sooooooo much money in keeping people sick. Spices are essential to natural health.
So is eating right, not smoking, not drinking (although I love my drinks).
I use to shake and barely be able to use my hands for writing, tying on flies you name it. Took myself off all the medicine and went to the spices and there is zero shaking, queezies none of it.
I’m borderline diabetic now. Your approach interests me.
How unpatriotic of you!
Do you realize how much profit you are denying the pigs at big pharma?
Hope you are using the water soluble form of cinnamon (cinnulin PF). Regular cinnamon has some toxic effects in large doses. Cinnulin PF is available at many online vitamin and supplement suppliers, such as Swanson and Puritan’s Pride (I think that’s the name).
Hey if they were making stuff that works and has the customers best interest in mind I wouldn’t have a problem but when everything you get for diabetes from them comes with a 6 page disclaimer? There’s this red flag that goes up with fireworks and spotlights.
I agree about the drugs. You might find this of interest:
http://abcnews.go.com/Health/story?id=3232247&page=1#.UCnOsqBFrE0
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.