Scientists show how fatty diets cause diabetes

August 14, 2011, Sanford-Burnham Medical Research Institute
Overnutrition in the Western world has led to an epidemic of type 2 diabetes. Credit: Peter Allen, University of California, Santa Barbara

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 , 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 , 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 for glucose using glucose transporters anchored in their . When 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.

High-fat diet and obesity cause beta cells to lose their ability to sense glucose in the blood. Left: Pancreatic beta cells from a mouse on a standard diet. Right: Pancreatic beta cells from a mouse fed a high-fat diet. (green=glucose transporters, red=insulin, blue=DNA) Credit: Marth laboratory, Sanford-Burnham/UCSB

In this newly discovered pathway, high levels of fat were found to interfere with two key —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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13 comments

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Stugoda
not rated yet Aug 14, 2011
I've often wondered whether artificial sugars can mess up our body's ability to react properly to the food we eat. I do my best to avoid them but, their increased use and the increase of these conditions seems to hint at a possible link.
kochevnik
1 / 5 (1) Aug 14, 2011
"Over-nutrition?" Westerners are starved for basic nutrition with mineral-depleted soils, impervious plasticized cell membranes from trans-fats, cancer-causing iodine deficiency from a brominated bread diet, and insecticide sweeteners. People in Africa are often much healthier, with a full set of teeth.
Canman
5 / 5 (1) Aug 14, 2011
Yes, over nutrition. You have to be blind to miss the difference between Americans and Africans (or most other non North American population). Americans, on the whole, are much fatter than people living in other countries. The root cause of type two diabetes is not beta cell dysfunction in the presence of high serum lipids; the cause is the American Diet. Type II diabetes is dramatically lower in Japan, rural India, France, and so on and so on. You could point to increasing levels of type II diabetes in these countries, but it is only in response to their importing a North American style diet. Why would we spend literally billions on the next diabetes "blockbuster drug" when the answer is on our doorstep? Here it is: beans, legumes, whole grains, nuts, fruits, vegetables, moderate canola and olive oil. Cut the animal sources. Research shows animal-sources of protein contribute to metabolic syndrome. Would save this country literally trillions in entitlement spending.
Canman
not rated yet Aug 14, 2011
Let's say this elucidated mechanism is developed into a new drug to fight off type II diabetes. Now we will have fat Americans who have decent blood sugars, but there plasma lipids will still be awful. Will still have all kinds of problems with strokes, heart attacks, colon cancer, and load bearing joint problems. Just google "plant based diet" or "vegan diet" and "cancer" or "diabetes" or "stroke" or "cardiovascular". All the information is out there!!!!!!
Canman
not rated yet Aug 14, 2011
Just ask Dr. Oz or Dr. Dean Ornish!!! No Brainer!!!
sstritt
not rated yet Aug 14, 2011
Its the carbohydrates stupid! (article, not previous comments)
Canman
not rated yet Aug 14, 2011
Yes it's the carbs, but not just the carbs. Look at China, where rice has been a staple for centuries. Only in the last decade has type II diabetes become a problem:

http://www.diabet...ina.html
Canman
not rated yet Aug 14, 2011
This is a good link to see how type II diabetes can be controlled with diet. It also mentions controlling other cardiovascular risk factors.

http://www.physic...Care.pdf

This took me 10 seconds to find. There are hundreds of articles like this
socean
not rated yet Aug 14, 2011
It is not ignorance of better diets that causes obesity and consequently diseases like diabetes. We like to eat some things that are not good for us, and we like to eat them in large enough quantities to cause problems.

We have two options: mitigate the behaviors or mitigate the consequences.

This research falls into the second category. Which is better than nothing.

We also need ways to change people's preferences. This is a lot more difficult it seems. But perhaps not impossible. Why, exactly, do we like fatty foods? What can we do to cause people to want to reject them? Better yet, what can we do to cause people to crave and eat foods that are healthier?

Where's my pill that makes me crave broccoli?

_nigmatic10
5 / 5 (1) Aug 15, 2011
Change the policies that govern the industries that govern the peoples diet choices. Put a leash on the policies that are encouraging raids on small health foods companies.
rawa1
not rated yet Aug 15, 2011
The smokers and fat people are actually saving healthcare system. They die earlier, before they can use it.

http://www.nytime...884.html

It can serve as an argument against additional taxes for unhealthy food. Not only this unhealthy food is generally cheaper to produce - it even saves a governmental health and life-insurance system...

http://www.nytime...tml?_r=1
Shamus123
not rated yet Aug 18, 2011
rawa, seriously? you dont think they are being provided healthcare in abundance for YEARS before they die??? Tard.
ROBTHEGOB
not rated yet Aug 21, 2011
Canman: Type 2 diabetes started to appear in China about the same time as McDonalds did. DUH!!!

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