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Researchers May Have Found Cause of Type 2 Diabetes
ozmanjusri writes "Scientists at Sydney's Garvan Institute have identified an enzyme called PKCepsilon as the active agent that blocks the production of insulin in diabetics. Insulin injections and implants try to control levels but do not address the reasons why insulin production is failing. This discovery may allow pharmaceutical companies to develop a drug to block the enzyme, allowing cells in the pancreas to function normally, though the team's leader, Trevor Biden, says 'What we've identified is a target that we can now latch onto to get therapy, but the journey from target to tablet of course is a long one ... It's probably going to take another 10 years at least to get something that's effective in humans.'"
Yes, but would they actually do that? There's a hell of a lot more money to be made by treating the symptoms, rather than curing the disease.
...Rob
The American Dream isn't an SUV and a house in the suburbs; it's Don't Tread On Me.
"We need 5L of patent applications, stat! Can you imagine the dough we'll make when we lock up this discovery so that no one else can cure diabetes but us?"
Seems like whenever the thought of "a Cure" or extremely important treatment comes up, its always 10 years away. When I first got type 1 diabetes they estimated that a cure would be ready in 10 years (This is 10 years ago), and my doctor also promptly told me that that is what they had said 10 years earlier. Every year now or so if I bother to try and keep up on whats new with diabetes, all I see is "d00dz 10 years till we got us a cure!". Diabetes, keeping funding and grants in pockets of people 10 years at a time, for the past 40 years.
I guess "being overweight and unhealthy" wasn't scientific enough.
On the one hand, I always like to see things cured. On the other hand, my fear of type II diabetes is one of those things that gets my ass out of bed in the morning, makes me walk to lunch, makes me have an apple instead of a twinky.
It like if they came up with a wonder pill that fixed all the bad cardiovascular problems you get from eating all the wrong stuff, a diet pill that keeps you from gaining any weight, and a cure for type II diabetes...I'm just not sure that would really be good for anyone. You should ahve to have some consequences.
I understand that there are those who get Type II through no fault of their own, and this makes me happy for them...But they're the minority, and I don't have as much sympathy for the rest.
ad logicam Claiming a proposition is false because it was presented as the conclusion of a fallacious argument.
people eat like shit and don't exercise. That's it. Pretty simple huh? Fiances father got diagnose with type 2 diabetes. Effecting him pretty badly for a year. Decides to eat healthy, drop weight, and exercise. Guess what happened? He is healthy now, no issues. You read tons of studies saying the same thing.
But that isn't profitable to companies....
Let me be the first to inform you that the number of countries where food is expensive and scarce has declined to a point where you can almost count them on the fingers of your two hands. Over-eating is a major problem in the poor world. Poor people are more likely to have serious problems, which means that they are more likely to eat for comfort. Also, poor people are more likely to have less knowledge about good nutrition.
Diabetes is on its way to becoming a poor man's disease. A cheap medicine against diabetes might do miracles for people in the developing countries a couple of decades from now.
It's not from being a fat-ass, it's from being a victim of food! The food is leaping off the plate...
You do realize that there is a lot of money to be made in preventive medicines of which this would be one. I doubt that they could cure it but removing the need for insulin would be a major benefit to both consumer and drug companies. My mom receives her insulin via overnight shipment - the packaging weighs many multiples compared to what was shipped. If its delivered improperly someone else eats the cost... meaning you and me. If the pharms could elminate medicines that require special handling it saves them money too.
Besides, giving a choice between paying for insulin, needles, blood test kits, or just a pill I know which I would take. I'd also be thankful someone is making it then going all tinfoil over their supposed real goals of keeping me sick - sick people die and don't buy more drugs - get over that
* Winners compare their achievements to their goals, losers compare theirs to that of others.
Unfortunately, you've got this wrong. Type II Diabetes is a failure of equilibrium functionality, not a case of hyperactivity of equilibrium mechanisms in the body. The body works to maintain equilibrium by releasing insulin following consumption of a meal, which in turn tells the cells of the body (primarily skeletal muscle cells) to take up glucose from the bloodstream. Type II diabetes, at its core, is a syndrome of insulin resistance, not a syndrome in insulin insufficiency. The skeletal muscle cells become less attentive to insulin signalling and refuse to take up glucose from the bloodstream in response to normal insulin levels within the body. The pancreas attempts to compensate by up-regulating the insulin thermostat, producing more and more insulin to try to get the muscles to respond by taking up the glucose. Glucose, if not taken up rapidly by the body's cells, can be harmful as it results in glycosylation of proteins all over the body (including in hemoglobin, in the form of HbA1C, which is a useful marker for long-term diabetes management analysis). The muscles become less willing to respond to the increased doses of insulin produced by the pancreas. Eventually, if not managed carefully, the pancreas may "burn itself out" - producing sub-normal levels of insulin, causing a type II diabetic to become insulin-injection dependent.
This research is incredibly interesting since it may reverse the burn-out syndrome and alleviate the need for poorly managed type II diabetics to inject insulin. It will not, however, reverse the insulin resistance present in insulin-sensitive cells within the body.
This is because after years of consistent overeating, your body begins to believe that elevated levels of blood sugar is "normal" and there is no need to produce more insulin.
This isn't true.
There are 2 components to type 2 diabetes
1) Insulin Resistance - Body isn't able to use the insulin produced efficiently.
2) Insulin Production - Body isn't able to produce enough insulin.
Here is the typical progression of type 2 diabetes.
For a normal person, when he eats carbohydrates, his blood sugar goes up. In response,
the pancreas produces insulin. The insulin pushes the blood sugar into the cells & the blood
sugar goes down.
When a person has insulin resistance, his pancreas produces insulin, but this insulin isn't
used efficiently. The insulin isn't able to push all the sugar into the cells. Hence the blood
sugar level doesn't go down immediatelly. Hence all the body parts are soaked in sugar which
is harmful to the organs. The pancreas is also an organ. The pancreas is soaked in sugar. This
causes insulin producing cells in the pancreas to die. This is a cyclic process i.e. because some
insulin producing cells die, the pancreases produces less insulin - this in turn causes blood
sugar to rise even more, which in turn causes more damage to the pancreas. This process keeps
continuing & finally when the pancreas has lost more than 50% of it's insulin producing cells,
blood sugar starts going out of control & he gets diabetes.
Typically, people who get type 2 diabetes are people who have the gene for
Insulin Resistance.
There are many people how much ever they eat, they don't get diabetes, or they
get it at a very advance age. Excess weight increases Insulin Resistance, but is
not the the cause of it.
A person with IR can delay or avoid diabetes for a long time by eating less, but
eating alone isn't the cause of type 2 diabetes.
Klinger you're right on the ball. I logged in to say exactly what you did. Type II diabetes is a failure of insulin signalling at the target tissues (liver, fat, muscle). Some people, particularly those exposed to high levels of insulin over a prolonged period (think fat or refined sugar eaters), downregulate the way their tissues respond to insulin. This means they are less effective at clearing glucose from the blood. To compensate for the elevated glucose levels, the pancreas secretes more insulin. At some point, the pancreas can no longer secrete enough insulin to lower the blood sugar and diabetes is diagnosed. In fact, the disease process had been ongoing for months to years prior to the person having high blood-sugar levels. Since islet cell shut down in the pancreas is one mechanism by which insulin levels become insufficient, an inhibitor of PKCepsilon may prevent this form happening. The diagnostic criteria of elevated blood-sugar may then not be recahed and, in that sense, a case of diabetes prevented or delayed. The underlying insulin resistance syndrome will still persist, therefore this drug does not treat the ultimate cause of Type II diabetes. As a pill, it would be a perfect drug company product. It would replace an injectable, need to be taken lifelong, used for a disease that is rapidly rising in incidence, and the drug would be patentable ($$$). The caveat is that PKC is a fairly important kinase. Off-target side effects could be prohibitive to drug development.
"It isn't just a genetic predisposition. There is a proven link between obesity and type 2. "
Did you think that you have the link backwards?
Yes people that get type 2 do often have trouble with weight. Ever think that the genetic predisposition might just cause that problem with it also contributes to that tendency to be over weight? BTW it isn't just being over weight. It is a specific body type that get is. People that tend to put on weight all over don't seem to get type 2. People that put weight on around the middle do!
Yes it is a genetic predispositions. With a very good diet and exercise if you have that disposition you may put it off until old age or maybe never. But there are many genetic issues that can helped by lifestyle changes and not just diabetes. That is why it is a predisposition. Depending on the gene load it may be treatable with just diet and exersice or it may not be.
But to blame it on gulttiony is ignorant and cruel.
See my blog http://ilovecookes.blogspot.com/ for light hearted technical information.
For those looking for the Cliff's Notes version of the parent:
The article got the types of diabetes wrong. Type 2 diabetes means the body can't use the insulin it has, not that it doesn't produce enough. For those who have Type 2 diabetes a long time, they may eventually need to inject insulin, and this discovery could prevent that from becoming necessray.
[Summarized by a Type 2]
I use irony whenever I can, but my shirts are still wrinkled...
That's right. My understanding is that diabetes type II is not a problem of the pancreas producing too little insulin, but of the muscle cells and fat cells not responding to insulin properly. But that's not what the investigators are saying. http://www.garvan.org.au/news-events/news/solving-a-critical-part-of-the-insulin-puzzle.html
Interestingly, the journal Cell Metabolism http://www.cellmetabolism.org/ which published the Australian paper http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413107002574 has another article in the current issue http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413107002598 by Chinese scientists about another protein, SIRT1, which regulates insulin resistance by the target cells.
Cell Metabolism, Vol 6, 320-328, 03 October 2007
Short Article
Inhibition of PKC? Improves Glucose-Stimulated Insulin Secretion and Reduces Insulin Clearance
Carsten Schmitz-Peiffer,1, D. Ross Laybutt,1 James G. Burchfield,1 Ebru Gurisik,1 Sakura Narasimhan,1 Christopher J. Mitchell,1 David J. Pedersen,1 Uschi Braun,2 Gregory J. Cooney,1 Michael Leitges,2 and Trevor J. Biden1,
1 Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
2 Biotechnology Centre of Oslo, University of Oslo, Oslo N-0317, Norway
Corresponding author
Carsten Schmitz-Peiffer
c.schmitz-peiffer@garvan.org.au
Corresponding author
Trevor J. Biden
t.biden@garvan.org.au
Summary
In type 2 diabetes, pancreatic ? cells fail to secrete sufficient insulin to overcome peripheral insulin resistance. Intracellular lipid accumulation contributes to ? cell failure through poorly defined mechanisms. Here we report a role for the lipid-regulated protein kinase C isoform PKC? in ? cell dysfunction. Deletion of PKC? augmented insulin secretion and prevented glucose intolerance in fat-fed mice. Importantly, a PKC?-inhibitory peptide improved insulin availability and glucose tolerance in db/db mice with preexisting diabetes. Functional ablation of PKC? selectively enhanced insulin release ex vivo from diabetic or lipid-pretreated islets and optimized the glucose-regulated lipid partitioning that amplifies the secretory response. Independently, PKC? deletion also augmented insulin availability by reducing both whole-body insulin clearance and insulin uptake by hepatocytes. Our findings implicate PKC? in the etiology of ? cell dysfunction and highlight that enhancement of insulin availability, through separate effects on liver and ? cells, provides a rationale for inhibiting PKC? to treat type 2 diabetes.
Cell Metabolism, Vol 6, 307-319, 03 October 2007
Article
SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B
Cheng Sun,1 Fang Zhang,1 Xinjian Ge,1 Tingting Yan,1 Xingmiao Chen,1 Xianglin Shi,1 and Qiwei Zhai1,
1 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Corresponding author
Qiwei Zhai
qwzhai@sibs.ac.cn
Summary
Insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes. SIRT1 has been reported to be involved in the processes of glucose metabolism and insulin secretion. However, whether SIRT1 is directly involved in insulin sensitivity is still largely unknown. Here we show that SIRT1 is downregulated in insulin-resistant cells and tissues and that knockdown or inhibition of SIRT1 induces insulin resistance. Furthermore, increased expression of SIRT1 improved insulin sensitivity, especially under insulin-resistant
Ok. So Doctors are people too. People with consciences. If a Doctor comes up with a promising cure to Diabetes, there is no corporate ethos in the world that will stop him from developing it.
One of my professors is a radiologist. One day at a banquet, he was seated next to a woman who was DEAD certain that there was a very simple cure to cancer that had already been discovered and that people like him were keeping it hidden so that they could make boatloads of money. After holding his tongue for half an hour, he replied "My mother died of Cancer."
I'm a 50 year old type 2 diabetic. I weigh 210 lbs, have a 34 inch waist, and stand 6'1", can bench press more than my body weight, and run an average of 12-14 Miles/week. Even in this condition, I have to use an oral medication (Glucophage) to fully control my blood sugar.
When I was first diagnosed, I had let myself get out of shape, and weighed about 225. I had to use insulin for about six months until I built enough muscle and lost enough fat to go to just oral meds, and for the first year after that, I had to take several.
I was in the army for 13 years when I was younger, and among other posts held the position of physical fitness instructor. I routinely scored on the extended scale in the APFT (Army Physical Fitness Test) every 6 Months for 8 to 10 years. (Basically, a Soldier had to score above 150 to finish basic training, extended scale starts with scoring over 100 in all three events - if you fall short in one, the high scores in the other two don't count). Getting back in shape with Diabetes was harder for me than getting to the top 2% of the Army. (And I had rank by then, so it wasn't drill sergeants pushing me, either).
I was never an Airborne Ranger, but I know a type 2 Diabetic who was, and he says getting back in shape felt about like Hell Week in ranger training (but lasted several months in his case).
There are several studies that show type 2 diabetes actually resets the satiation levels of the brain so that people with it get hungrier and have longer before they register fullness when their blood sugar levels are off (The disease thus impairs your judgment of one of means to fight it). There are others that show how a normal person will have extreme soreness the first few exercise sessions but if they push through it will stop feeling nearly that sore and how the average Type 2 Diabetic can expect that to continue for months or even more.
(It was about 6 months in my case - six months of near constant fatigue and extreme muscle soreness - six months when I did 8 reps with a weight, then 2 days later did the same 8 reps, then 2 days later did the same 8 reps, only to gain a rep every 2-3 weeks, before the process started getting up to normal sorts of gains - six months of worrying I would injure a foot with all the running and they would do what frequently happens to diabetics - amputation!).
Comments like yours are every bit as untrue and abusive as telling a rape victim they deserved it because they were dressed wrong. You should be heartily ashamed. It's not the researchers who 'just don't get it' here, it's people like you.
Who is John Cabal?
I'd say that, far more than people realize, health problems can be nailed down to nutritional issues. I don't mean "too much fat" or that sort of thing. People suffer weird symptoms from specific vitamin deficiencies and the like.
For instance, I know one person who suffered from "hypothyroidism" for a long time and had to take T4 supplements. It turned out that her real problem was an iodine deficiency, that itself was likely caused by being on the birth control pill. Taking high doses of an iodine supplement cleared up the problem very quickly, and her thyroid began functioning properly again.
I know another patient who was inexplicably ill for many years. After an IgG panel blood test, it was determined that she had a food alergy to casein, the principal protein in milk and other dairy derivatives. This isn't the sort of IgE alergy that causes itching or anaphalaxis, but the IgG kind that takes days to set in, and the symptoms are less severe and can be flu-like. Part of the reason she never considered cutting out dairy was that she is not, in fact, lactose intolerant, so lactase ensyme didn't help. Eliminating dairy entirely solved her problem.
Just like the preceding case, I have an IgG reaction to soy protein. Imagine trying to avoid soy in the U.S. Soybean oil is the default "vegetable oil," soya lecithin is used as an emusifier in lots of foods, and soy protein isolate (not considered to be a food by the FDA) is added to lots of things that want to report having high protein content. Oh, and don't forget the estrogen analogues found in soy. Anyhow, challenging as it was, eliminating soy products resulted in a huge improvement to my energy level. (I suffer from chronic fatigue syndrome, and my nutritionist believes that it was caused by the soy alergy compromising my immune system.)
I know lots of people who have suffered from prolonged illness that was completely blown off by MDs that was then remedied very quickly by a nutritionist. And it frustrates me to no end how ignorant MDs are about nutritional effects and that they never refer people to nutritionists!
Ok, so what's my point? That in a lot of cases, I would not be surprised of there was some kind of food that people are sensitive to or which is eaten to excess that has compromised part of their metabolism. Taking insulin shots was a bandaid for diabetics. Taking something to inhibit PKCepsilon production is a BETTER bandaid, but it's still a bandaid. Someone's got to figure out the root cause.
Oh, did you know that a significant number of autism cases, when caught early enough, show remarkable improvement when wheat and dairy are removed from their diets? Many neurologists will tell you otherwise, but that's because they just don't study nutrition in school. The nutritionists know otherwise.
Oh, and BTW, I'm not against MDs. I just know their limitations. Got a broken bone, lyme disease, or a structural organ failure? Better go to an MD. But many of the little things that affect people's health are not in the "take this pill" or "let me operate" categories but rather in the "don't eat this" and "eat this instead" categories. The effect of environment and intake has a HUGE impact on the human body!
is overconsumption of refined carbohydrates. This causes an insulin overproduction and consequential insulin resistance and tiring of the pancreas. If type II diabetes were not caused by diet, then why does it respond so well to a low carbohydrate diet? All symptoms disappear. This indicates that it is not a permanent condition but one brought on by the sufferers own dietary habits. See the following: "the Cure for Diabetes" in Men's Health http://www.menshealth.com/cda/article.do?site=MensHealth&channel=health&category=other.diseases.ailments&conitem=4a935e4e40fae010VgnVCM20000012281eac____
Now we just need someone to invent PKUnCepsilon.
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