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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.'"
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.
The Garvan Institute is a non-profit organisation. They do patent discoveries, but any income earned is used to fund other research projects.
"I've got more toys than Teruhisa Kitahara."
Isn't type 2 diabetes basically dietary related (adult onset) and controled by monitoring blood sugar while type 1 is the permanent loss of pancreatic beta cells that produce insulin, which I guess is what your mom has? If so then this research wouldn't help people like your mom since they have no insulin in the first place.
It is by the juice of the coffee bean that thoughts acquire speed, the teeth acquire stains. The stains become a warning
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.
This is the current received wisdom. The article mentions research leading another way. Basically it says you need fat + a certain enzyme to develop Diabetes Type 2. This may or not be true, but it's certainly worth investigating.
From the FA In their study, the researchers used genetically modified mice to observe the link between an oversupply of fat and type 2 diabetes.They found mice without the enzyme did not develop diabetes, despite gaining weight on a high-fat diet.
That would at least explain why some people can be as fat as they like without ever developing Diabetes 2 and why Diabetes 2 seems to run in families.
-- Put crudely, the world is an extremely large problem instance. (Russel/Norvig Artificial Intelligence)
Almost all cases of T2D are curable by a lifestyle change.
Wrong.
It's controllable by a lifestyle change.
Not curable.
My husband used to take your basic 70/30 mix (generic). In order to improve his sugar control, his doctor eventually switched him to a combination of Lantus and Humalog (both still brand-name only from what I can tell). Unfortunately, we discovered some time after that that Lantus is hard on the kidneys. With his kidneys already declining in function (common in diabetics), the doctor switched out the Lantus for old-school NPH (generic) with Humalog.
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
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?