Re: Mice with diabetes suddenly didn't have diabetes any more.

[Guest guest]

Hmmm, well, people have been espousing the healing benefits of red pepper for ages. So perhaps it's a little of both? Systemic and local? My guess though, is that an injection to the immediate site will produce bigger results. I have to warn you all. If you use the cream, even if you think you've washed it off your hands, you may pick it up again from one of the areas you applied it to. I woke up the other morning rubbing my eye and ended up feeling like I'd been pepper sprayed! It was really bad, couldn't open my eye for close to an hour. So use extreme caution when using capsaicin cream. The residue packs a punch for a long time. penny Nelly Pointis <janel@...> wrote: Since reading this article a couple of days ago, I have been trying to figure out whether capsaicin gets absorbed systemically or whether it has to be injected to the site of the inflammation to produce this effect. If anybody has the answer... Nelly (...)Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas.(...) (...)that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn's disease.(...) Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an "enormous" number of nerves, pain neurons primarily used to signal the brain that tissue has been

damaged.Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick -- injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes.(...) So next they injected the neuropeptide "substance P" in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.The islet

inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one injection. http://www.canada.com/nationalpost/news/story.html?id=a042812e-492c-4f07-8245-8a598ab5d1bf & k=63970 & p=1 Diabetes breakthroughToronto scientists cure disease in mice Tom Blackwell, National PostPublished: Friday, December 15, 2006In a discovery that has stunned even those behind it, scientists at a Toronto hospital say they have proof the body's nervous system helps trigger diabetes, opening the door to a potential near-cure of the disease that affects millions of Canadians.Diabetic mice became healthy virtually overnight after researchers injected a substance to counteract the effect of malfunctioning pain neurons in the pancreas."I couldn't believe it," said Dr.

Salter, a pain expert at the Hospital for Sick Children and one of the scientists. "Mice with diabetes suddenly didn't have diabetes any more."The researchers caution they have yet to confirm their findings in people, but say they expect results from human studies within a year or so. Any treatment that may emerge to help at least some patients would likely be years away from hitting the market.But the excitement of the team from Sick Kids, whose work is being published today in the journal Cell, is almost palpable."I've never seen anything like it," said Dr. Hans Dosch, an immunologist at the hospital and a leader of the studies. "In my

career, this is unique."Their conclusions upset conventional wisdom that Type 1 diabetes, the most serious form of the illness that typically first appears in childhood, was solely caused by auto-immune responses -- the body's immune system turning on itself.They also conclude that there are far more similarities than previously thought between Type 1 and Type 2 diabetes, and that nerves likely play a role in other chronic inflammatory conditions, such as asthma and Crohn's disease.The "paradigm-changing" study opens "a novel, exciting door to address one of the diseases with large societal impact," said Dr. Christian Stohler, a leading U.S.

pain specialist and dean of dentistry at the University of land, who has reviewed the work."The treatment and diagnosis of neuropathic diseases is poised to take a dramatic leap forward because of the impressive research."About two million Canadians suffer from diabetes, 10% of them with Type 1, contributing to 41,000 deaths a year.Insulin replacement therapy is the only treatment of Type 1, and cannot prevent many of the side effects, from heart attacks to kidney failure.In Type 1 diabetes, the pancreas does not produce enough insulin to shift glucose into the cells that need it. In Type 2 diabetes, the

insulin that is produced is not used effectively -- something called insulin resistance -- also resulting in poor absorption of glucose.The problems stem partly from inflammation -- and eventual death -- of insulin-producing islet cells in the pancreas.Dr. Dosch had concluded in a 1999 paper that there were surprising similarities between diabetes and multiple sclerosis, a central nervous system disease. His interest was also piqued by the presence around the insulin-producing islets of an "enormous" number of nerves, pain neurons primarily used to signal the brain that tissue has been damaged.Suspecting a link between the nerves and diabetes, he and Dr. Salter used an old experimental trick

-- injecting capsaicin, the active ingredient in hot chili peppers, to kill the pancreatic sensory nerves in mice that had an equivalent of Type 1 diabetes. ToolsPage 2 Tom Blackwell, National PostPublished: Friday, December 15, 2006"Then we had the biggest shock of our lives," Dr. Dosch said. Almost immediately, the islets began producing insulin normally "It was a shock ? really out of left field, because nothing in the literature was

saying anything about this."It turns out the nerves secrete neuropeptides that are instrumental in the proper functioning of the islets. Further study by the team, which also involved the University of Calgary and the Laboratory in Maine, found that the nerves in diabetic mice were releasing too little of the neuropeptides, resulting in a "vicious cycle" of stress on the islets.So next they injected the neuropeptide "substance P" in the pancreases of diabetic mice, a demanding task given the tiny size of the rodent organs. The results were dramatic.The islet inflammation cleared up and the diabetes was gone. Some have remained in that state for as long as four months, with just one

injection.They also discovered that their treatments curbed the insulin resistance that is the hallmark of Type 2 diabetes, and that insulin resistance is a major factor in Type 1 diabetes, suggesting the two illnesses are quite similar.While pain scientists have been receptive to the research, immunologists have voiced skepticism at the idea of the nervous system playing such a major role in the disease. Editors of Cell put the Toronto researchers through vigorous review to prove the validity of their conclusions, though an editorial in the publication gives a positive review of the work."It will no doubt cause a great deal of consternation," said Dr. Salter about his paper.The researchers are now setting out to confirm that the connection between sensory nerves and diabetes holds true in humans. If it does, they will see if their treatments have the same effects on people as they did on mice.Nothing is for sure, but "there is a great deal of promise," Dr. Salter said.© National Post 2006

[Guest guest]

This article is confusing to me. If injecting substance P works

because the pain (that should have been there) signals the body to

fix the problem, then why does killing the pancreatic sensory nerves

with capsaicin work too? I missed the logic (gee, it's a good thing I

wasn't the researcher....)

- Kate

On Dec 18, 2006, at 12:11 PM, Penny Houle wrote:

> Nelly Pointis <janel@...> wrote:

> Since reading this article a couple of days ago, I have been trying

> to figure out whether capsaicin gets absorbed systemically or

> whether it has to be injected to the site of the inflammation to

> produce this effect.

>>

>> (...)Diabetic mice became healthy virtually overnight after

>> researchers injected a substance to counteract the effect of

>> malfunctioning pain neurons in the pancreas.(...)

>>

>> Suspecting a link between the nerves and diabetes, he and Dr.

>> Salter used an old experimental trick -- injecting capsaicin, the

>> active ingredient in hot chili peppers, to kill the pancreatic

>> sensory nerves in mice that had an equivalent of Type 1 diabetes.

>> (...)

>>

>> So next they injected the neuropeptide " substance P " in the

>> pancreases of diabetic mice, a demanding task given the tiny size

>> of the rodent organs. The results were dramatic.

>> The islet inflammation cleared up and the diabetes was gone. Some

>> have remained in that state for as long as four months, with just

>> one injection.

>

[Guest guest]

http://www.cell.com/content/article/fulltext?uid=PIIS0092867406014656

See if reading the full article helps

Nelly

Re: [infections] "Mice with diabetes suddenly didn't have diabetes any more."

This article is confusing to me. If injecting substance P works because the pain (that should have been there) signals the body to fix the problem, then why does killing the pancreatic sensory nerves with capsaicin work too? I missed the logic (gee, it's a good thing I wasn't the researcher....)- KateOn Dec 18, 2006, at 12:11 PM, Penny Houle wrote:> Nelly Pointis <janelpiedbauge (DOT) net> wrote:> Since reading this article a couple of days ago, I have been trying > to figure out whether capsaicin gets absorbed systemically or > whether it has to be injected to the site of the inflammation to > produce this effect.>>>> (...)Diabetic mice became healthy virtually overnight after >> researchers injected a substance to counteract the effect of >> malfunctioning pain neurons in the pancreas.(...)>>>> Suspecting a link between the nerves and diabetes, he and Dr. >> Salter used an old experimental trick -- injecting capsaicin, the >> active ingredient in hot chili peppers, to kill the pancreatic >> sensory nerves in mice that had an equivalent of Type 1 diabetes. >> (...)>>>> So next they injected the neuropeptide "substance P" in the >> pancreases of diabetic mice, a demanding task given the tiny size >> of the rodent organs. The results were dramatic.>> The islet inflammation cleared up and the diabetes was gone. Some >> have remained in that state for as long as four months, with just >> one injection.>

[Guest guest]

A caveat: I'm not 100% confident I'm reading this paper well. I

certainly have never read any mammal genetics of this complexity.

*All* this stuff hinges on TRPV1(NOD), the version of the TRPV1

protein found in the NOD mouse lineage, which is mutated and seems to

function abnormally.

What's fascinating is that TRPV1 has nothing to do with the immune

system proper. If you fix the TRPV1 problem in the mice by adding the

unmutated TRPV1 gene back in (I wasn't clear on precisely in what way

that was done), the lymphocytes from those mice can still cause

diabetes1 when transfered to NOD.scid mice (which are diabetes-prone

NOD mice that can't develop diabetes on their own, because they have

no lymphocytes). So, NOD mice may have something wrong with their

immune system, but apparantly that's not really enough to cause

pancreatitits (the main cause of diabetes1) unless they ALSO have

this abnormality of sensory neurons.

Basically, this will turn out to be a landmark study if and only if

TRPV1 mutations are involved in human diabetes, other diabetes1

models, or other diseases. TRPV1 is found in a few other disease-

associated loci (stretches of genes), as they note at the end of the

paper. (I'm guessing the diseases in question there are model ones.)

Obviously, the first thing that will be checked is whether humans

with diabetes1 also have a mutant TRPV1 protein. If so, it will be on

the front page of newspapers and the whole thing will be Nobel

material. If not, it's still a very interesting thing in principle,

and serves to underline that we may never comprehend certain

inflammatory diseases by looking just at the immune system proper -

that's something which is already highlighted by the lateral symmetry

of lesions quite often seen in rheumatoid arthritis and scleroderma

(ie, the same joints lesioned on both sides of the body).