Posted on 08/14/2011 12:29:12 PM PDT by decimon
High levels of fat shut down a key enzyme that promotes glucose sensing in pancreatic beta cells -- revealing a pathway implicated in the type 2 diabetes epidemic
SANTA BARBARA, Calif., August 14, 2011 – Newly diagnosed type 2 diabetics tend to have one thing in common: obesity. Exactly how diet and obesity trigger diabetes has long been the subject of intense scientific research. A new study led by Jamey D. Marth, Ph.D., director of the Center for Nanomedicine, a collaboration between the University of California, Santa Barbara and Sanford-Burnham Medical Research Institute (Sanford-Burnham), has revealed a pathway that links high-fat diets to a sequence of molecular events responsible for the onset and severity of diabetes. These findings were published online August 14 in Nature Medicine.
In studies spanning mice and humans, Dr. Marth's team discovered a pathway to disease that is activated in pancreatic beta cells, and then leads to metabolic defects in other organs and tissues, including the liver, muscle and adipose (fat). Together, this adds up to diabetes.
"We were initially surprised to learn how much the pancreatic beta cell contributes to the onset and severity of diabetes," said Dr. Marth."The observation that beta cell malfunction significantly contributes to multiple disease signs, including insulin resistance, was unexpected. We noted, however, that studies from other laboratories published over the past few decades had alluded to this possibility."
In healthy people, pancreatic beta cells monitor the bloodstream for glucose using glucose transporters anchored in their cellular membranes. When blood glucose is high, such as after a meal, beta cells take in this additional glucose and respond by secreting insulin in a timed and measured response. In turn, insulin stimulates other cells in the body to take up glucose, a nutrient they need to produce energy.
In this newly discovered pathway, high levels of fat were found to interfere with two key transcription factors—proteins that switch genes on and off. These transcription factors, FOXA2 and HNF1A, are normally required for the production of an enzyme called GnT-4a glycosyltransferase that modifies proteins with a particular glycan (polysaccharide or sugar) structure. Proper retention of glucose transporters in the cell membrane depends on this modification, but when FOXA2 and HNF1A aren't working properly, GnT-4a's function is greatly diminished. So when the researchers fed otherwise normal mice a high-fat diet, they found that the animals' beta cells could not sense and respond to blood glucose. Preservation of GnT-4a function was able to block the onset of diabetes, even in obese animals. Diminished glucose sensing by beta cells was shown to be an important determinant of disease onset and severity.
"Now that we know more fully how states of over-nutrition can lead to type 2 diabetes, we can see more clearly how to intervene," Dr. Marth said. He and his colleagues are now considering various methods to augment beta cell GnT-4a enzyme activity in humans, as a means to prevent and possibly cure type 2 diabetes.
"The identification of the molecular players in this pathway to diabetes suggests new therapeutic targets and approaches towards developing an effective preventative or perhaps curative treatment," Dr. Marth continued. "This may be accomplished by beta cell gene therapy or by drugs that interfere with this pathway in order to maintain normal beta cell function."
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In the United States, more than 24 million children and adults—nearly eight percent of the population—have diabetes. In adults, type 2 diabetes accounts for about 90 to 95 percent of all diagnosed cases of diabetes. This study was primarily funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). Co-authors of this study include Kazuaki Ohtsubo at Sanford-Burnham and Mark Z. Chen and Jerrold M. Olefsky from the University of California, San Diego.
For more information about Sanford-Burnham research, visit our blog (http://beaker.sanfordburnham.org) or follow us on Twitter (http://twitter.com/SanfordBurnham).
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.
About Center for Nanomedicine
The Center for Nanomedicine (CNM) is a collaborative partnership that leverages and synergizes the expertise of two world-renowned institutions, Sanford-Burnham Medical Research Institute (Sanford-Burnham) and the University of California, Santa Barbara (UCSB). This model of collaboration brings together Sanford-Burnham's biomedical research capabilities and UCSB's biomedical engineering. The partnership creates fertile ground for developing the next generation of effective disease diagnostics and therapeutics.
;-)
Rats! I was hoping you would tell me I was wrong about beer. I loves me some beer.
Rats! I was hoping you would tell me I was wrong about beer. I loves me some beer.
So if you eat 2,000 cals a day then you can probably have two beers once in awhile. That is my recipe and I am doing great(and I loves me some beer too).
FReepmail me if you want on or off the diabetes ping list. If you enter Volek JS, Feinman RD into PubMed's query box, then you'll do an authors' search on two writers who have written at least 10 articles showing the benefit of carbohydrate restriction.
Lard makes the absolute best fried chicken. I only do it a couple of times a year, but man, it’s so good.
YES....what you said....there’s a fast food joint around here that sells the low carb burger, and it’s REALLY good....big ole crisp lettuce leaf wrapped around a hamburger with tomato and onion....YUM
Well, good for you. No one says that attempting to control carbohydrate intake is forbidden for type II diabetics. That is a good thing. What this study states is that apparently fat intake is a key to producing type II diabetes in rats. The implication is that humans should react similarly. I am type II. My mother and every one of her siblings were/are type II. My father is not. He has a sweet tooth. Everyday he has ice cream with granola on it and he also likes breads. So apparently type II diabetes is a bit more complex than simply intake of sugar.
This “study” is nonsense.
Use of the wrong fats causes type II diabetes.
Canola oil, soy oil, safflower oil, cotton oil, all lead to insullin resistance by altering the fat chemistry of the cell membranes, making it impossible for cells to receive insullin.
Changing over to Coconut oil, beef tallow, flax oil, and olive oil will correct the cell membrane chemistry.
http://www.cancertutor.com/Diabetes/Diabetes_Type_II.htm
>> “First, from my read of this paper, the connection being made is between obesity and diabetes. A fatty diet was used to cause obesity, and then diabetes developed.” <<
.
This is an absolute falsehood.
Obesity can result from diabetes, but diabetes cannot result from obesity.
Diabetes cannot happen unless the membranes of your cells become impermeable. The fats that make cell membranes impermeable cannot come from your own body, because the have to be unsaturated fats to cause that change.
Only vegetable oils can cause type II diabetes.
http://www.cancertutor.com/Diabetes/Diabetes_Type_II.htm
Whole wheat bread is not healthy.
Eliminating as much of your grain consumption as possible will go a long way toward improving your health. The oils and proteins in grains are difficult for the body to utilize.
Nuts are a far better source if you are insistant on vegetation, but really, meats are the best answer.
>> “OTOH I think coconut oil is one of the healthiest foods on the planet.” <<
.
Lots of truth to that.
Both for curing type II diabetes, and for dementia/Alzheimers, coconut oil is a strong player.
Nothing out of a box, can or bag is a good rule of thumb. Of course, there are exceptions, such as sardines, which are one of the highest quality foods available.
“I use portabella mushroom caps as burger buns.”
How does that taste? My problem with trying to eat low carb is that I just hate the substitutes for breads, etc. I have tried the low carb tortillas and would rather not eat a tortilla at all if that is all I can have. Also, when I go to a restaurant, it seems that all I can get is a salad with meat topping (such as a Cobb salad).
I keep trying to stick to a low carb diet and keep failing.
I love 'em, but then, I've always been a mushroom eater. Try this...do your regular burger. Top it with some crumbles bleu chees, some buffalo wing sauce and a few jalapeno slices. I could eat those every day :-)
It is hard to break the carb cycle initially, but this was my experience: I went absolutely cold turkey on carbs. No bread, no rice, no potatoes, no pasta, etc. After about 2-3 days, I realized how accustomed I'd become to feeling bloated because I just didn't feel bloated anymore. The hard part was knowing when I was truly hungry, because for a while, my body was confusing the absence of bloat with hunger! When I didn't feel bloated I was motivated to eat so I would feel like my body was accustomed to feeling. With a little self-discipline, and after a week or so carb free, I found I was eating a lot less of everything because I was simply no longer confusing healthy hunger with the unhealthy need to stuff myself.
Also, when I was eating a lot of carbs I would have to pretty much take a pepcid or other antacid every day. Since I cut them out altogether I've had no such need (and I eat a lot of spicy foods).
Now I'll occasionally indulge in some carbs, but try to restrict it to whole grains when possible...If your experience mirrors mine, I think you'll find that with a very rigorous denial for about a week or so, you'll find that you'll lose a lot of the desire and hunger for carbs.
I will try to be genteel here, but some people (my husband included) experience some gastro upset problems (frequent trips to the bathroom or the opposite) when they eat low carb. Since you went cold turkey on carbs, did you have any problems, and, if so, how did you deal with that?
(you can send me a private message if this is getting to be TMI for most Freepers)
I started with a 24 hour fast, but intentionally started that by purging with a bunch of dried apricots and apple cider...so...yeah, there was some self induced gastro upset for the first day or so. Just make sure you get plenty of water so you don't dehydrate. I then went for a lot of fish, jerky, chicken breasts, cheese, etc. as well as all the veggies I wanted, and slowly ramped up the quantities.
I haven't had any issues (apart from those first 24 hours or so :-)
Grapeseed oil, too...
I use worcestshire or some sauce (salt/pepper, etc) on portabella’s and then grill or saute them in oil....then use as burger bun...kinda messy, but yummy...
Grapeseed oil is a bit of a fad right now, so the price is way out of line with the benefit.
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