Clues seen to how fructose may promote diabetes

NEW YORK (Reuters Health) – A new animal study may help explain why diets high in the sugar fructose have been linked to insulin resistance, a precursor to type 2 diabetes.

Scientists found that a particular gene, known as PGC-1 beta, appears to play a key role in the development of insulin resistance in response to a high-fructose diet. Rats that had the gene's activity blocked were protected from insulin resistance despite feasting on a diet loaded with fructose.

A sweetener known as high-fructose corn syrup has been widely used in sodas and processed foods since the 1980s, and some researchers have blamed this trend at least in part for the concurrent rise in obesity and diabetes.

The authors of the current report, in the journal Cell Metabolism, explain that some studies have shown that fructose is metabolized differently than glucose is, being more readily converted into fat.

Other studies have linked diets heavy in high-fructose corn syrup to elevated risks of high triglycerides (a type of blood fat), fat buildup in the liver, and insulin resistance, note Dr. Gerald Shulman and colleagues at Yale University School of Medicine.

For their study on the genetic underpinnings of fructose-induce insulin resistance, they zeroed in on PGC-1 beta because it activates another gene that governs the production of fat by the liver.

When the researchers blocked the gene's activity in rats fed a high-fructose diet, the animals did not develop insulin resistance and elevated triglycerides.

The implication, according to Shulman's team, is that inhibiting PGC-1 beta could help treat some cases of high triglycerides, fatty liver disease and insulin resistance. Much more research remains to be done, however.

SOURCE: Cell Metabolism, March 4, 2009.

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Or....we could just not eat fructose. Duh.

--Melissa

But, what would we do with all that corn?

Make ethanol. All cars since 1989 have sophisticated enough computers to run on a 50/50 mix of ethanol/gasoline without modification. Brasil has been running virtually all of it's cars on a 97/3 mixture since ~1990.

http://www.eurekalert.org/pub_relea...p-mlb022409.php

A new study in mice sheds light on the insulin resistance that can come from diets loaded with high-fructose corn syrup, a sweetener found in most sodas and many other processed foods. The report in the March issue of Cell Metabolism, a Cell Press publication, also suggests a way to prevent those ill effects.

The researchers showed that mice on a high-fructose diet were protected from insulin resistance when a gene known as transcriptional coactivator PPARg coactivator-1b (PGC-1b) was "knocked down" in the animals' liver and fat tissue. PGC-1b coactivates a number of transcription factors that control the activity of other genes, including one responsible for building fat in the liver.

"There has been a remarkable increase in consumption of high-fructose corn syrup," said Gerald Shulman of Yale University School of Medicine. "Fructose is much more readily metabolized to fat in the liver than glucose is and in the process can lead to nonalcoholic fatty liver disease," he continued. NAFLD in turn leads to hepatic insulin resistance and type II diabetes.

Metabolic syndrome and type 2 diabetes have both reached epidemic proportions worldwide with the global adoption of the westernized diet along with increased consumption of fructose, stemming from the wide and increasing use of high-fructose corn syrup sweeteners, the researchers noted.

High-fructose corn syrup, which is a mixture of the simple sugars fructose and glucose, came into use in the 1970s and by 2005 the average American was consuming about 60 pounds of it per year. Overall, dietary intake of fructose, which is also a component of table sugar, has increased by an estimated 20 to 40 percent in the last thirty years.

Earlier studies had established that fructose is more readily converted to fatty acids than glucose and had also linked high-fructose diets to high blood levels of triglycerides (a condition known as hypertriglyceridemia), NAFLD and insulin resistance. While researchers had implicated a gene known as SREBP-1, a master regulator of lipids' manufacture in the liver, much about the underlying molecular connections between fructose and those metabolic disorders remained mysterious.

In the new study, the researchers zeroed in on PGC-1b, a gene known for boosting SREBP-1 levels. To test its role in the effects of fructose, they blocked its activity in mice fed a diet high in that sugar for four weeks.

Those treatments improved the animals' metabolic profiles by lowering levels of SREBP-1 and other fat-building genes in their livers. The mice also showed a reversal of their fructose-induced insulin resistance and a threefold increase in glucose uptake in their fat tissue.

"These data support an important role for PGC-1b in the pathogenesis of fructose-induced insulin resistance and suggest that PGC-1b inhibition may be a therapeutic target for treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis," the researchers concluded.

The new study has "revealed the transcriptional coactivator PGC-1b as a missing link between fructose intake and metabolic disorders," wrote Carlos Hernandez and Jiandie Lin of the University of Michigan Medical Center, Ann Arbor in an accompanying commentary. "The findings …support the emerging role of gene/environment interaction in modulating the metabolic phenotype and disease pathogenesis. Thus, perturbations of the same regulatory motif may produce vastly different metabolic responses, depending on the specific combinations of dietary nutrients," they continued.

Does this study on diet soft drinks vs ones with fructose mean that we could see a surge of normal weight people with Type 2 diabeties?

http://www.webmd.com/diet/news/2005...ain-more-weight

I think it's another screwy bit of reasoning. When do people generally switch from full-sugar soft drinks to diet soft drinks? When they gain weight obviously. So, obviously the association goes up as you gain weight. Does that mean that the diet soft drink caused the weight gain?

It's like reasoning that buying size 16 pants causes weight gain because the people who do buy them are fat.

I agree! And it is an assumption still to say that overweight causes type II diabetes. Maybe the same thing that causes the obesity causes diabetes. Or, maybe, just maybe, the diabetes causes the obesity...

I suspect I am hypoglycemic. I haven't been tested by a doctor, I score at risk on the online test http://www.hypoglycemia.org/hypo_test.asp My score was 104. I am fairly sure that having to eat so frequently on top of fairly large meals caused my obesity. If I had been steered toward LCing, this might have been avoided. I don't think that drinking diet soda caused me to be obese or even crave food, I think my high carb/low fat diet did that. Still, I have to wonder if a lot of thin people that drink regular sodas are heading for trouble unaware, because they aren't overweight.

I see a t-shirt in the making a picture of an ear of corn on a car and under it- it says GOT FUEL? in smaller letters it says corn is for cars not humans.

Hey. Once the lo-carb/hi-fat paradigm finally takes hold we could... I dunno, how about... FEEDING IT TO THE COWS!

Er, corn ain't so great for them either. Pollan's, the Omnivores Delemma, is a great read -- although he comes some wrong conclusions,

Niether is being eaten But, I do love some hamburgers.

Where do I sign up for this T-Shirt?????
Seriously, great idea! But I do miss corn on the cob loaded with butter at the summer bbq's.

How many times do they have to replicate research conducted back in the 80s which showed how dangerous that fructose is?