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Decreasing insulin resistance prevents obesity-related cardiovascular damage
Date:2/11/2009

has decreased ability to use or discard the fuel. To make matters work, PTP1B is over-expressed in obesity, further hampering the body's ability to deal with glucose by inappropriately turning off insulin receptors. "You have lost your thermostat."

High glucose levels also mean higher levels of super oxides that block nitric oxide, MCG researchers say. "Once you have less nitric oxide, you start getting blood vessel disease," says Dr. David Fulton, vascular biologist at the Vascular Biology Center and senior investigator on the grant. Blood vessels stop dilating as they should, walls become inflamed and thick and clots can form. "You start adding up cardiovascular problems," says Dr. Fulton, associate professor in the MCG Schools of Medicine and Graduate Studies.

"What this gene is telling us is, if you can just improve the fine control, the fact that your fasting glucose is a little off, despite the fact that you are still fat, your cardiovascular function is enormously better," Dr. Stepp says.

Nitric oxide is like a tonic for keeping the cardiovascular system healthy, the researchers say, and nitric oxide levels are an "early casualty" of swinging glucose levels. Obese mice show impaired nitric oxide dilation, a defect corrected by deleting PTP1B. Obese humans also show evidence of impaired blood vessel dilation and vascular remodeling. In an effort to figure out how, the researchers will look at blood flow, blood pressure and vascular remodeling in the PTP1B knockout mice. They want to identify aspects of nitric oxide signaling impaired in obesity and improved with reduced insulin resistance.

"We are trying to identify the molecular mechanisms of cardiovascular disease associated with obesity and track that with improvements in insulin resistance," Dr. Stepp says.

One of the body's natural responses to high glucose levels sugar sticking to hemoglobin may be the best measure of swinging glucose levels that need to
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert

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