Skip to comments.Suspected cause of type 1 diabetes caught "red-handed" for the first time
Posted on 05/10/2008 4:36:30 PM PDT by neverdem
Michael Purdy Senior Medical Sciences Writer firstname.lastname@example.org (314) 286-0122
Scientists at Washington University School of Medicine in St. Louis working with diabetic mice have examined in unprecedented detail the immune cells long thought to be responsible for type 1 diabetes.
Researchers were able to examine the immune cells from isolated insulin-making structures in the pancreas known as the islets of Langerhans. They caught the immune cells, known as dendritic cells, "red-handed" carrying insulin and fragments of insulin-producing cells known as beta cells. This can be the first step toward starting a misdirected immune system attack that destroys the beta cells, preventing the body from making insulin and causing type 1 diabetes.
The results, reported online in The Proceedings of the National Academy of Sciences, push scientists a step closer to finding ways to treat this condition.
"Now that we've isolated dendritic cells from the pancreas, we can look at why they get into the pancreas and determine which of the materials that they pick up are most critical to causing this form of diabetes," says senior author Emil R. Unanue, M.D., the Paul and Ellen Lacy Professor of Pathology. "That may allow us to find ways to inhibit dendritic cell function in order to block the disorder."
The American Diabetes Association estimates that 1 million to 2 million Americans suffer from type 1 diabetes, which is also called juvenile diabetes because it frequently develops in children.
Patients require insulin injections to survive because the immune system has destroyed the islets of Langerhans, which contain the body's only beta cells. The insulin these cells make is required for the critical task of regulating blood sugar levels.
Scientists detected dendritic cells in the islets years ago. Dendritic and other antigen-presenting cells are the sentinels of the immune system: They pick up bits of protein from around the body and present them to lymphocytes to initiate an immune system reaction. The lymphocytes lead immune attacks against foreign invaders like bacteria and viruses and eliminate them, clearing infections. But when interaction between an antigen-presenting cell and a lymphocyte leads to a part of the body being mistakenly identified as alien, the resulting attack harms the body, causing autoimmune diseases.
Although dendritic cells' presence in the islets and their ability to summon immune attacks made them likely suspects in type 1 diabetes, they were challenging to isolate from the pancreas for closer examination.
"They're very tiny and there are only about 5 to 10 of them per islet, each of which contains approximately a thousand cells," explains Unanue. "So the senior postdoctoral researcher in the lab who did this work, Boris Calderon, had to develop some sophisticated cellular assays to pick them up."
Calderon, M.D., found indications that the cells were carrying granules of insulin and pieces of proteins from beta cells on their cell surfaces. To test whether this cargo carried by the dendritic cells had the potential to trigger an immune attack on beta cells, Calderon exposed the dendritic cells to lymphocytes taken from diabetic mice. The lymphocytes were activated by the dendritic cells of the islets and switched into attack mode.
In a separate line of research, Unanue's lab has learned that dendritic cells in the pancreas may normally have beneficial effects on the health of beta cells. They've shown that when dendritic cells are absent from the pancreas, the beta cells are smaller, an indication that they're not as healthy.
"We think these dendritic cells aren't in the pancreas by accident," says Unanue. "We believe that in the normal individual they help maintain the health of beta cells. But in a person with autoimmune diabetes, they appear to start the problems that destroy beta cells."
The key distinction likely lies in a group of proteins called the major histocompatibility complex (MHC). Two decades ago, Unanue and Paul Allen, Ph.D., the Robert L. Kroc Professor of Pathology and Immunology, showed that the MHC provides the stage on which antigen-presenting cells show bits of protein or peptides to other immune system cells. Scientists believe autoimmune conditions like type 1 diabetes are caused by differences in what the MHC binds to and how it presents that material to immune attack cells. In support of this theory, Unanue's laboratory and that of Michael Gross, Ph.D., Washington University professor of chemistry, have collaboratively shown that the genes that encode the MHC proteins in the diabetic mouse are unique and bind to a set of very characteristic peptides.
In addition to studying what protein fragments carried by dendritic cells are essential for causing type 1 diabetes, Unanue and others are working to learn how genetic variations in the MHC alter the chances that the immune system will mistakenly attack the body.
Calderon B, Suri A, Miller MJ, Unanue ER. Dendritic cells in islets of Langerhans constitutively present beta cell derived peptides bound to their class II MHC molecules. Proceedings of the National Academy of Sciences, early online edition.
Funding from the National Institutes of Health, the Juvenile Diabetic Research Foundation, and the Kilo Diabetes and Vascular Research Foundation supported this research.
Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
The article title over-sells the incomplete state of their knowledge.
According to the late Dr. Robert C Atkins there is already a cure for juvenile diabetes, at least in some cases:
“To give you the flavor of the exhilarating satisfaction I get from practicing this new kind of medicine; listen to the story of my patient Marie Speller. An eleven-year-old who had been recently diagnosed with juvenile diabetes, she had been prescribed two varieties of insulin. Doctors are traditionally taught that juvenile diabetes carries with it a life sentence requiring insulin. However, I had learned from treating other diabetic patients that if one of the lesser-known vita-nutrients, calcium AEP, is given during the first year of this illness, the illness can be reversed. I put Marie on a vita-nutrient program, and we were able to lower her insulin dose, week by week, until six months later she stopped taking the drug completely. Her blood sugar levels were virtually normal and have remained so for the past two years, at which time her pancreas responded to a carbohydrate meal with a normal output of insulin.”
from “Dr. Atkins’ Vita-Nutrient Solution : Nature’s Answer to Drugs” by Robert C. Atkins, M.D.
Ah, the far-flung Isles of Langerhans...
IMHO, I think it is more likely the kid had a genetic variant for MODY, Maturity Onset Diabetes of the Young.
Dendrites are parts of neurons, the main cells in the nervous system. These are dendritic cells, sentinels in the immune system.
Dendritic cells play a critical role in a number of immunological processes. These recently described cells function as potent antigen presenting cells, act as stimulators of a mixed lymphocyte reaction, and serve as passenger cells that elicit rejection of transplanted tissues. They originate from the bone marrow, sojourn in the blood, and reside in the tissues. Two aspects of dendritic cells are being studied: differentiation from bone marrow in vitro and ability to function as antigen presenting cells in a number of tissues. Under the influence of granulocyte/macrophage colony stimulating factor (GM-CSF), dendritic cells differentiate from bone marrow precursors over 4-5 days of culture in a serum-free medium. For both rat and mouse, dendritic cells produced in culture differ functionally and phenotypically from their precursors. Studies using monoclonal antibodies and functional assays are aimed at delineating the differentiation pathway and establishing the relationship between dendritic cells and other bone marrow-derived cell types. In addition, dendritic cells are being studied in the eye and lung where special immunological conditions exist. Immune responses do not always occur when antigens are introduced into these tissues, even though dendritic cells are present. We are interested in determining how the immune responses are controlled.
“IMHO, I think it is more likely the kid had a genetic variant for MODY, Maturity Onset Diabetes of the Young.”
That’s very interesting. Calcium AEP is known to have a therapeutic effect on other auto-immune disorders, such as MS, so the truth is uncertain. If the medical profession were rational healers they would resolve the ambiguity by intensively testing this otherwise harmless substance. But alas, that is not the world we live in.
I suspect this problem is being caused by the vaccination of children at such a young age.
I suspect it is more likely linked with developmental immunotoxicity events (prenatally) among susceptible genotypes. For example Heilmann et al. PLoS Medicine August 2006 shows how even childhood vaccine responses at age seven are more directly influenced by cord blood toxicant (in that case PCBs) levels than the blood levels occurring at age seven at the time of the vaccination. So earlier events can establish the subsequent childhood immune dysfunction.
I used to work with a woman that could list off the nutritional supplement cure for practically any malady, including type 1 diabetes. Really annoying. I learned to never discuss health issues of any kind with her. For every disease or disorder out there, including mental ones, somebody is convinced there is a nutritional cure for it.
Why? Do you have evidence of an increase in the incidence of type 1 diabetes over time?
And they usually believe that the nutritional cure has been SUPPRESSED by GREEDY BIG PHARMA so they can rack up OBSCENE PROFITS selling their POISONS to the victim-public.
“For every disease or disorder out there, including mental ones, somebody is convinced there is a nutritional cure for it.”
It really doesn’t matter what someone thinks, it matters what is really true. Doctors tell me that nutritional cures are “not proven medicine”, but they don’t say that no one will ever spend the money to prove them, because it just isn’t profitable. Seeing is believing, and when you see as I have someone given up for dead by conventional medicine come back to life with nutritional treatment, you know, not guess, that there is something to it. It doesn’t always work; nothing does!
“2000 IUs of Vitamin D”
That’s very interesting.
Vitamin D is shaping up as the cure-all of the 21st century:
The National Institutes of Health (NIH)[http://www.nih.gov/] funded part of this diabetes study. The NIH is part of the Department of Health and Human Services which funds Medicare and about half of Medicaid as well as part of the Child Health Insurance Program. If there was so much to all these nutritional cures, the feds would be jumping all over themselves to fund the studies if there was any potential to save money.
“If there was so much to all these nutritional cures, the feds would be jumping all over themselves to fund the studies if there was any potential to save money.”
You’d think that they’d want to, but they don’t.
For instance, a nutritional cure for multiple sclerosis was published in 1973 by Dr. Frederich R. Klenner, BS, MS, MD. Dr. Klenner was a graduate of the Duke University medical school, and was a Fellow of The American College of Chest Physicians; Fellow & Diplomate: The International College of Applied Nutrition; Fellow: The American Association for the Advancment of Science; Fellow: The American College of Angiology; Fellow: The American Academy of Family Practice; Fellow: The Royal Society of Health (London); Fellow (Honorary): The International Academy of Preventive and Orthomolecular Medicine; Fellow: International College of Angiology; and Founder-Fellow: American Geriatrics Society.
In the “Conclusions” of this paper he states the following:
“We categorically make this statement: Any victim of Multiple Sclerosis who will dramatically flush with the use of nicotinic acid, and who has not yet progressed to the stage of myelin degeneration, as witnessed by sustained ankle clonus elicited in the orthodox manner, can be cured with the adequate employment of Thiamin Hydrochloride and other factors of the Vitamin B Complex in conjunction with essential proteins, lipids, carbohydrates and injectable crude liver. If sustained ankle clonus is not bilateral, then it is not a deterrent. We have had patients who did demonstrate bilateral sustained ankle clonus, and who were in wheelchairs, and who returned to normal activities after 5 to 8 years of treatment.”
I probably wouldn’t believe this bizarre state of affairs myself, if I hadn’t had my eyes opened by personal experiences in my own life.
"Injectable crude liver" sounds off the wall. It looks like he never submitted his paper to a peer reviewed journal.
Enter Klenner F or Klenner FR into PubMed. That's the way to do an author search at PubMed.
There's no citation for 1973. F.R. Klenner had four citations between 1949 - 1952. One included MS and the other three included vitamins.
If you bothered to look at the link you’d know it was published in “Journal of Applied Nutrition”.
This is a “catch 22”. If the more mainstream medical journals refused to publish nutritional cures, how does that then become a reasonable criterion of correctness?
Here is a biography of Dr, Klenner, for anyone who is interested. The article in Wikipedia on Dr. Klenner was recently deleted on someone’s request. Apparently the war to suppress nutritional medicine continues! The work of men like Fred Klenner stands as an indictment of mainstream medicine, and they don’t want to ever have to deal with it.
Anyone who wants themselves and their families to die of diseases that were cured 35 years ago is welcome to do whatever they want.
We honeymooned there.
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