AUGUSTA, Ga. - Knocking out one gene that contributes to insulin resistance appears to prevent much of the cardiovascular damage typically associated with obesity, researchers say.
Cardiovascular disease is the biggest health threat of obesity and Medical College of Georgia researchers trying to understand why have knocked out protein tyrosine phosphatase 1B, or PTP1B, in genetically fat mice that get diabetes.
"Even before you have really bad diabetes, you are walking around obese with your glucose control a little bit off and already beating up your circulation," says Dr. David Stepp, vascular biologist at the MCG Vascular Biology Center and co-director of MCG's Diabetes & Obesity Discovery Institute. "That is the point where you need to be intervening."
If he's right, PTP1B becomes a drug target for obese people who may not yet be diabetic but already have trouble with blood glucose control.
"We have shown cardiovascular function is improved by knocking out this gene. The question is why," says Dr. Stepp, principal investigator on five-year, $2.5 million National Institutes of Health grant that he hopes will help find the answer.
He suspects resistance may again be the problem but this time it's to nitric oxide, a powerful dilator of blood vessels.
Overeating increases glucose so the body increases insulin production in an effort to use or store this important energy source. In people headed toward diabetes, the body begins to miscalculate insulin needs and overproduce; fine control is lost and the high and low insulin swings begin.
"If you are obese, the fasting glucose may be a little bit off but not terrible. What is terrible is you are beginning to lose control," says Dr. Stepp, associate professor in the MCG Schools of Medicine and Graduate Studies. Over time, the body gets in the vicious cycle of making more insulin and paying less attention to it. Blood glucose levels soar while the body
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Medical College of Georgia