Type 2 Diabetes: Genes Linked To Insulin Resistance Identified

University of Alabama at Birmingham via ScienceDaily ^ | October 27, 2007 | NA

[neverdem]

New research from University of Alabama at Birmingham identifies two genes that may play a role in insulin resistance, opening a new avenue for researchers searching for treatments for type 2 diabetes and metabolic syndrome. The UAB team found that two genes, NR4A3 and NR4A1, seem to boost insulin sensitivity in muscle tissue.

Insulin lowers blood glucose, or sugar, by moving it from the bloodstream into skeletal muscle, where it is metabolized for energy or stored for later use. Type 2 diabetes results from either a shortage of insulin or from de-sensitized muscle that does not respond well to insulin, allowing elevated glucose levels to remain in the blood stream. This latter defect is called insulin resistance.

“Our findings* show that these two proteins help sensitize muscle to insulin, promoting glucose uptake and thus keeping glucose levels within healthy limits,” said W. Timothy Garvey, M.D., professor and chair of the Department of Nutrition Sciences at UAB and the lead investigator of the study. “This gives science a new target for diabetes research by suggesting new pathways for drug development that will help boost the presence or activity of NR4A3 and NR4A1.”

Garvey and colleague Yuchang Fu, Ph.D., assistant professor of nutrition sciences, also found that both genes were under-expressed in animal models with diabetes, leading to increased insulin resistance.

“In simple terms, the abundant presence of these proteins in the body is a positive factor for avoiding diabetes, while their absence is associated with increased incidence of the disease,” Garvey said. “By better understanding the biologic underpinnings of the disease, we can begin to find novel therapeutic targets to decrease insulin resistance.”

Garvey said the next step will be a methodical search of promising molecules that may interact with and promote the presence of NR4A3 and NR4A1.

There are more than 20 million Americans living with diabetes, 7 percent of the population. According to the National Institutes of Health, the incidence of diabetes is likely to increase due to the aging U.S. population and to the prevalence of obesity in America, both of which are risk factors for diabetes.

According to recent estimates from the Centers for Disease Control and Prevention, diabetes will affect one in three people born in 2000 in the United States. The prevalence of diagnosed diabetes in the United States is expected to increase 165 percent by 2050. Diabetes is widely recognized as one of the leading causes of death and disability in America.

These findings were published recently in the Journal of Biological Chemistry.

Adapted from materials provided by University of Alabama at Birmingham.

[muawiyah]

This is an article about genes. You either have them or you don't. Getting fat will not create nor destroy your genes.

Now that we're past the propaganda part of this marginally researched story, we might imagine the researchers will next examine WHY some folks have alleles of these two genes that don't produce the protein necessary for metabolising insulin.

I'm just guessing it's going to be that same minority group, the hunters, gatherers and herdsmen who have all the rest of the pre-starch/sugar/agriculture characteristics.

[Viking2002]

Interesting. I'm Type II (maternally inherited - my mother's side of the family are all diabetic, going back generations). I was able to get off the Glucovance two years ago thru a combination of diet modification and exercise. I just have to stick myself twice a week, and get my A1C checked quarterly. This would be good news for anyone who might be at risk in the future - I can tell you from personal experience, if it isn't caught and dealt with at the onset, it will leave it's permanent calling card. And like my doctor said, there's no being 'kinda' diabetic, like there's no being 'kinda' pregnant. Once you have it, you have it. (Hey, I went through that whole Kubler/Ross cycle when I got diagnosed, too.)

[Straight Vermonter]

ping

[muawiyah]

The underlying cause is genetic. You had it the day you were conceived. On the other hand, Type II diabetes is not a “disease” if you lead the correct lifestyle ~ which seems to include an almost exclusive fish, meat and low starch rootcrop diet, at the top of mountains, with miles and miles of walking, lots of other exercise, running with the dog-team, chasing reindeer, chasing wildabeast, hunting seal on Arctic pack-ice, and avoiding anything else except for tree nut oils.

[bmwcyle]

ping

[Viking2002]

I never said it was a 'disease' in the classical sense of it being pathogenically induced. You otherwise reinforced my point - if you have the genetic predisposition for it, the best way to combat it is thru diet and exercise. And it takes a pretty radical change in lifestyle to do it - most people would rather pop pills and live a more sedentary lifestyle. But, I'm not one to do that and cry 'woe is me' over it. I knuckled down and kicked it's ass. It'll always be there, lurking, and waiting to pounce if I let my guard down, so it's a lifelong commitment. But it's a commitment that'll affect how long that life is.

[muawiyah]

Popping the pills doesn't necessarily make it go away either. Let's not mislead anyone about that. You have to exercise and control your diet to a degree most people probably think is impossible.

If we could just clear away this civilization debris moved in around the neighborhood by the agriculturalists, and turn it back into prime pastureland like God intended, I think it'd be easier!

[Viking2002]

I sit here as proof it is possible. And yes, it can be a pain in the ass to get to that point. But, through the more healthy diet, and sometimes inconvenient rigor of busting a good sweat three times a week, it helps guarantee that, God willing, I'll still have an ass that feels pain forty years from now. LOL

[neverdem]

NR4A Orphan Nuclear Receptors Modulate Insulin Action and the Glucose Transport System

FReepmail me if you want on or off of the diabetes ping list. I was asked to take over it. The former keeper thanked all of you for the good times. That's a link to the abstract, i.e. summary, of the original article.

[trisham]

Thanks for the ping!

[Jedi Master Pikachu]

"Getting fat will not create nor destroy your genes."

It might change whether or not those genes are expressed, though.

[muawiyah]

Well, it might and it might not. SOmetime before birth half your genes get shut down anyway ~ randomly ~ one strand here, the other strand there, etc.

Throughout your life you will lose cells of one or both varieties at different rates. Stuff can show up later on that was insignificant in your early years. Important stuff can disappear over the years.

Getting fat is symptomatic, not a cause, of diabetes Type II. Frequently folks gain a lot of weight long before they notice any other problem.

[SunkenCiv]

Thanks neverdem.