SEE SICK VESSELS: Diabetes deteriorates the small blood vessels found in the eyes, kidneys and around nerves.
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It is well known that diabetes wreaks havoc on the vascular system. In fact, vascular complications arising from diabetes are the leading cause of blindness, kidney failure and cardiovascular problems in the U.S. And yet, the physiological mechanisms that link diabetes, which afflicts 26 million Americans, to sickly blood vessels are poorly understood.
Researchers have now identified key interactions among two enzymes that may help connect the dots between insulin control and the integrity of blood vessels. The two enzymes work in tandem to regulate the production of nitric oxide, a gas that relaxes blood vessels. The findings, shown in mice, could provide targets for drugs that would be designed to prevent and offset vascular damage.
"Sadly, most people with diabetes will die from vascular complications," says Clay Semenkovich of Washington University in Saint Louis School of Medicine, co-author of the study published January 28 in The Journal of Biological Chemistry. Diabetes contributes to large blood vessel damage associated with common cardiovascular problems such as stroke and heart disease, but diabetes also deteriorates small blood vessels found in the eyes, kidneys and around nerves. "Small-vessel disease is fairly specific for diabetes, while large-vessel disease also occurs in people without diabetes, especially smokers," Semenkovich says.
As a metabolic disease, diabetes causes a cascade of problems, many linked to high blood levels of glucose and lipids. "Increased sugars and fats promote oxidative stress—the production of excessive amounts of oxygen-derived free radicals that can damage blood vessels," according to Semenkovich. The damage manifests as inflammation. Nitric oxide, produced by the enzyme nitric-oxide synthase (NOS), helps reduce inflammation. NOS functions, however, only when attached to a blood vessel's endothelium (inner membrane) by a common fatty acid called palmitate.
"This fatty acid is abundant, so it was assumed that NOS would use any available palmitate to anchor itself to the membrane," Semenkovich says. "Surprisingly, we found that this is not correct," Instead, the researchers found that NOS requires palmitate synthesized by the fatty-acid synthase (FAS), an enzyme that is regulated by insulin. Without FAS, NOS cannot properly attach to the endothelium. People with diabetes have low levels of FAS due to insulin deficiency or resistance, and this FAS deficit may be at the root of their increased vulnerability to blood vessel damage.
The researchers teased out the association by studying knockout mice (genetically engineered to turn off a specific gene) that lack FAS in their endothelial cells. These so-called FASTie mice had normal overall levels of NOS but were deficient in endothelium-attached NOS. Molecular studies confirmed that FAS and NOS physically bind to each other.
FASTie mice had "leaky" blood vessels and impaired angiogenesis, meaning they were less able to restore blood flow after injury to an artery. In people with diabetes defective angiogenesis is implicated in peripheral vascular disease, which often leads to limb amputations.
"These findings provide a surprisingly simple mechanism underlying blood vessel damage in diabetes," Semenkovich says. He suggests that restoring FAS activity would be a novel therapeutic approach to countering vascular damage in diabetes.
"The identification of new treatment for the vascular complications of diabetes is critical since the risk of developing diabetes is increasing at epidemic proportions," says George King, chief scientific officer for the Joslin Diabetes Center in Boston, who was not involved in the study. The role of FAS and lipid abnormalities is an "exciting new idea" in understanding endothelial dysfunction, according to King, but their specific contribution to the microvascular complications of diabetes is less clear.
There are steep hurdles to overcome in upgrading these proof-of-principle findings into therapeutic applications. The diabetic mouse model has not always translated well to humans, and commonly used knockout mice represent an extreme condition. The question remains, King says, "Can you make smaller changes and still be effective?"
What is clear is that the FAS–NOS mechanism is just one of multifarious contributing factors. In addition to investigating causal mechanisms, research teams are also studying protective agents, such as antioxidants, that help the body fight damage.
The difficulty in understanding and treating diabetes-related vascular disease reflects the labyrinthine complexity of diabetes itself. It is a disease that affects a large number of metabolites, which are the foundation of the body's fuels. On top of that, diabetes also affects many tissues, which handle fuel metabolism differently. "It is unlikely that one single pathway will cause all complications," King says.
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8 Comments
Add CommentWould it be unreasonable to provide diabetes sufferers with a supplimental NO inhaler (non-toxic levels, of course) similar to the oxygen inhalers currently available?
Reply | Report Abuse | Link to thisWouldn't it more reasonable to help diabetes sufferers with a more natural, i.e., not toxic, diet, which can actually cure them in many cases?
Reply | Report Abuse | Link to thisAfter all, it's the wrong fuel ( glucose concentrates) in the first place that our body was never meant to have to metabolize, and that's causing the tissue damage!
To use a simple analogy:
Put sugar in the fuel tank of your car, and then watch what happens!
see www.youthevity.com
The two deficient enzymes mentioned in the article are products of genes being read and proteins being synthesized. I am not aware of any dietary changes that diabetics could make that would improve this type of protein systhesis. Sunnystrobe do you have something specific in mind regarding diet? I am interested in any information you might have to offer.
Reply | Report Abuse | Link to thisDr. Cal
Dietary changes are the only remedy to tackle the epidemic increase of diabetes, since the problem that's causing it is clearly our nutritionally deficient feeding habits, mainly caused by our profit-biassed 'food' industry, with sugar-baited, animal-fat-laced, and salt-laden 'fast' food monstrosities that may taste 'moreish', but, through their energy concentration, are un-natural, but all the more highly addictive to our body system which can easily get out of sync at a cellular level, because the enzyme system gets overstressed with this synthezised 'Frankenstein food'.
Reply | Report Abuse | Link to thisWe happen to be the only mammals that invented 99% fatty foods like oil, margarine, butter, that, alas, lack the living fatty acids; we have increased our sugar intake a hundredfold -and with it our diabetes!- and we can claim that we alone invented 'combustion' ( which denatures proteins, depletes vitamins, and destroys living enzyme/co-enzyme proteins through massive heat damage.
How much more blithely ignorant can we get?
I am particularly astounded how many medical specialists & researchers appear to turn a blind eye to their own blatant case of mal-(='bad') nutrition, all in favour of finding a new pill as a magic bullet.
Yet it has been known for many decades now that a diet of enzyme-rich raw plant foods can prevent and/or reverse not only diabetes, but also cancers and heart disease, and arthritis, and osteoporosis, etc, etc.
I personally have met people who managed this 'self-cure' through simple diet changes, and compiled my own findings into a health almanac, after having run workshops at local community level, from which evolved the Y.AN.C.H.E.P. DI.E.T., as an easy, but species-specific nutrition alternative, fit for mankind and kind to women, because it minimizes cooking and favours salad days!
It deals with optimal food choices from a grassroot approach.
I would like to welcome you at our interactive www.Youthevity.com, or The Yanchep Diet, via Google.
Wow, SunnyStrobe, what a self-righteous, self-serving, and innaccurate diatribe you've written!
Reply | Report Abuse | Link to thisDiabetes--types 1 and 2--are complex conditions with different/many causes. And, there is absolutely no proof that merely eating salads and raw vegetables can cure any disease or condition or provide optimum health. Period.
I have two male relatives with type II diabetes. Both are tall and slender. Both are active guys. Neither has any known relatives with diabetes. And yet both were hit with it severely and suddenly. Both work hard at managing the disease, with excellent doctors providing treatments that include medication, nutritional plans, and excercise regimens.
Desipite all of this, one has PAD resulting in multiple arterial bypasses and amputations. The other did everything "right", but still needed to have a diabetes pump implanted to control his disease.
So, unless you earn an M.D. with a speciality in Endocrinology and can then speak intelligently about this awful disease, please be quiet.
A healthy diet may negate some diseases and/or delay others but just eating a certain way isn't a magic bullet either. Sometimes the damage is so severe that just a healthy lifestyle doesn't do the trick. I started improving my diet and getting more exercise in my late thirties. At fourty two I had a heart attack. My HDL cholesterol reading wasn't bad and the LDL cholesterol reading was above recommended but wasn't particularly high either. My blood pressure was so low that frequently they had to try several times to find it.
Reply | Report Abuse | Link to thisGenetics has a pretty profound impact. So does exposure to environmental toxins and various pathogens. I get a fairly large amount of exercise, cut way back on meat and cheese and stopped drinking milk entirely. I increased my intake of raw vegetables significantly. I regularly take flax seed oil and eat blueberries and almonds. The end result after several years post heart attack is that my HDL cholesterol is up only 2 points and my LDL is down to safe levels only from medication. My blood pressure has increased by about 20 points to the low end of the "normal" range.
Veggies are not a magic bullet any more than a pill is.
Know thyself, Abbie; methinks your diatribe against me is a clear case of the 'shooting-the-messenger' syndrome - and not quite fit to be texted in a scientific journal like S.A. !
Reply | Report Abuse | Link to thisI am sorry to hear about the two diabetes cases in your family; however, you have not mentioned anything about their PRE-diabetes II lifestyle/eating habits .
I would strongly recommend everyone still doubting the connection between nutrition and disease to read "The China Study" by Professor Colin Campbell.
We might want to blame our genes for our bodily shortcomings, but with optimal feeding schemes, we can definitely do our best to avert any unnecessary system breakdowns. (Any good vet would first ask: 'What has your dog been feeding on?')
Doctors are notorious for their ignorance concerning optimal nutrition, because they simply never had to study it to any length in medical school.
There's one good old Greek doctor Dr. Hippocrates of Cos, however, who is famous for his interest in nutrition as the no 1 healing factor:
'Let your FOOD be your MEDICINE!' this makes sense and has been thoroughly corroborated in the light of modern medical science; vide World Health Organization et al.
Call me 'self- centered & self- righteous' if you wish - but rest assured that , for me, after spending a dozen or more years on reading hundreds of books on the matter, I felt it was time to write a personal diet almanac,if only to let my friends and others know how relatively easy it can be to feel so much more healthy and happy.
You blame me for being 'inaccurate' - without mentioning any detail; I can assure you my findings are not a concoction of my own, but all firmly based on medical research publications over the last twenty years. See under youthevity.com
Thank you for your reply, how interesting that you got over your heart crisis so well; I am sure it's not 'only from medication' that your LDL is down- since you have cut down on the foreign- cholesterol culprits such as meat and cheese!
Reply | Report Abuse | Link to thisI had an aunt who had a life-threatening heart condition half a century ago,still aged under fifty; forty years later, as a still sprightly late octogenarian, she told me she owed her life to her German health practitioner
Dr. Max Otto Bruker whose advice was simply:
NOT to drink or eat anything that has been ADVERTISED, and to AVOID protein made TOXIC by COOKING.
She had a habit of starting her lunch with a delicious mixture of a freshly grated raw carrot and apple; I read that on this regime, blood pressure can be normalized naturally within three weeks. Surely it's worth trying out - since, unlike a pill, it will have no toxic & long term side effects.
Blueberries are all right for anthocyanins, but how about eating in all plant pigment colours on a daily basis -for even more complete health cover? (See under: Colour Eating Without heating, or Yanchep Diet)
Linseed taken as a cereal,(together with whole almonds and sunflower seeds), soaked overnight in its natural state ( NOT extracted and bottled, and therefore still nicely unoxidised and 'alive') is the highest omega- three- providing food. See :youthevity.com for recipe- it works!