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Enzymes may point toward better therapies for prediabetes
Date:12/13/2012

AUGUSTA, Ga. Two enzymes that are elevated in prediabetes could hold clues to helping the 79 million Americans with the condition avoid serious vascular complications and maybe even identify those most at risk for full-blown diabetes, researchers say.

The enzymes, arginase and indoleamine 2,3 dioxygenase, or IDO, also have in common degrading amino acids, responding to inflammation and suppressing immunity, said Dr. William Caldwell, Chair of the Department of Pharmacology and Toxicology at the Medical College of Georgia at Georgia Health Sciences University.

That common ground has a newly formed research team watching how and why these two enzymes increase and how they may contribute to vascular problems in both an animal model of diabetes and a cohort of prediabetic humans.

They theorize a vicious cycle where elevated glucose increases production of inflammatory factors like cytokines and reactive oxygen species which in turn elevate arginase and IDO. The latter then further elevates cytokines and reactive oxygen species which damage blood vessels.

"You just put cells in high glucose and they start producing reactive oxygen species and these cytokines. It's a toxic situation," said Caldwell, cardiovascular pharmacologist and a principal investigator on the one-year, $450,000 seed grant from National Institute of Diabetes and Digestive and Kidney Diseases.

The animal model deficient in the satiety hormone leptin and at risk for vascular dysfunction enables the researchers to watch the scenario play out from normal to prediabetic to diabetes.

As they find, for example, cytokines in the animal model, they look in the blood of obese prediabetic people to see if they also find them there, said Dr. Yanbin Dong, MCG geneticist, cardiologist and principal investigator. They've already documented significantly increased levels of proinflammatory cytokines in prediabetic individuals, said Dr. Rudolf Lucas, MC
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Contact: Toni Baker
tbaker@georgiahealth.edu
706-721-4421
Georgia Health Sciences University
Source:Eurekalert  

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